Clobazam
Identification
- Summary
Clobazam is a benzodiazepine used as adjunct treatment in seizures associated with Lennox-Gastaut syndrome.
- Brand Names
- Onfi, Sympazan
- Generic Name
- Clobazam
- DrugBank Accession Number
- DB00349
- Background
Clobazam belongs to the 1,5-benzodiazepine class of drugs and is marketed under different names, Onfi, Frisium, Urbanyl, and others.9. Clobazam was first synthesized in 1966 and first published in 1969, following the incidental synthesis and discovery of the first benzodiazepine chlordiazepoxide in the 1950s.12 Unlike older 1,4-benzodiazepines, clobazam has a better side-effects profile, particularly less sedative and amnesic effects.15,9 This is likely because of clobazam's higher affinity to the α2 subunit of the GABAA receptor, which mediates anxiolytic effects, than the α1 subunit, which mediates sedative effect.9 Additionally, clobazam is believed to be a partial agonist to the GABAA receptor rather than non-selective full receptor agonists like 1,4-benzodiazepines, thus potentially explaining the decreased incidence of sedative effects.16,17
Clobazam has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984.1,2 In October 21, 2011, the FDA approved clobazam as an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in adults and children aged two years and older.14 In 2005, clobazam also received approval from Health Canada as an add-on therapy for generalized tonic-clonic, myoclonic, and focal impaired awareness seizures.18
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
- Weight
- Average: 300.74
Monoisotopic: 300.066555377 - Chemical Formula
- C16H13ClN2O2
- Synonyms
- 1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepine
- 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione
- Clobazam
- Clobazamum
- External IDs
- H 4723
- H-4723
- HR 376
- HR-376
- LM 2717
- LM-2717
Pharmacology
- Indication
Clobazam is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.23
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Anxiety ••• ••••• Management of Catamenial epilepsy ••• ••••• Adjunct therapy in management of Refractory status epilepticus ••• ••••• Adjunct therapy in management of Seizures •••••••••••• ••• •••••••••• •••••••••• •••• •••••••••••••• ••••••• •••••• Adjunct therapy in management of Seizures •••••••••••• ••••••••••• •••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Clobazam belongs to the benzodiazepine class of drugs.23 Clobazam acts on the GABAA receptor to increase GABAnergic transmission, particularly chloride conductance in neurons.9 This causes neuronal hyperpolarization, resulting in an increase in the action potential threshold and reducing neuron firing frequency.11,12 Consequently, the general neuronal activity of the central nervous system is depressed; therefore, clobazam can be used to treat diseases caused by excessive excitatory action potentials.12
The effect of clobazam 20 mg and 80 mg administered twice daily on QTc interval was evaluated in a randomized, evaluator-blinded, placebo-, and active-controlled (moxifloxacin 400 mg) parallel thorough QT study in 280 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on the Fridericia correction method was below 10 ms, the threshold for regulatory concern. Thus, at a dose two times the maximum recommended dose, clobazam did not prolong the QTc interval to any clinically relevant extent.23
- Mechanism of action
The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve the potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor.23 Specifically, clobazam binds to the interface of the α2 and γ2-subunit of the GABAA receptor.9 It has a great affinity for the α2 subunit than the α1 subunit compared to other 1,4‐benzodiazepines.10Binding of clobazam to the GABAA receptor causes chloride channels to open, resulting in an influx of chloride and thus hyperpolarization of neurons.9
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - Absorption
The peak plasma levels (Cmax) and the area under the curve (AUC) of clobazam are dose-proportional over the dose range of 10-80 mg following single- or multiple-dose administration of ONFI. Based on a population pharmacokinetic analysis, the pharmacokinetics of clobazam are linear from 5-160 mg/day.23
Clobazam is rapidly and extensively absorbed following oral administration. The time to peak concentrations (Tmax) of clobazam tablets under fasted conditions ranged from 0.5 to 4 hours after single- or multiple-dose administrations. The relative bioavailability of clobazam tablets compared to an oral solution is approximately 100%. After single-dose administration of the oral suspension under fasted conditions, the Tmax ranged from 0.5 to 2 hours. Based on exposure (Cmax and AUC) of clobazam, clobazam tablets and suspension were shown to have similar bioavailability under fasted conditions. The administration of clobazam tablets with food or when crushed in applesauce does not affect absorption. Although not studied, the oral bioavailability of the oral suspension is unlikely to be affected under fed conditions.23
- Volume of distribution
Clobazam is lipophilic and distributes rapidly throughout the body. The apparent volume of distribution at steady state was approximately 100 L.23
- Protein binding
The in vitro plasma protein binding of clobazam and N-desmethylclobazam is approximately 80-90% and 70%, respectively.23
- Metabolism
Clobazam is extensively metabolized in the liver via N-demethylation and hydroxylation to form two major metabolites, N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, respectively, with approximately 2% of the dose recovered in urine and 1% in feces as an unchanged drug.23,13 The N-demethylation reaction is catalyzed primarily by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6. N-desmethylclobazam, an active metabolite, is the major circulating metabolite in humans, and at therapeutic doses, plasma concentrations are 3-5 times higher than those of the parent compound. Based on animal and in vitro receptor binding data, estimates of the relative potency of N-desmethylclobazam compared to the parent compound range from 1/5 to equal potency. N-desmethylclobazam is extensively hydroxylated, mainly by CYP2C19. N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine.23. The formation of 4'-hydroxyclobazam is facilitated by CYP2C18 and CYP2C19.13
The polymorphic CYP2C19 is the major contributor to the metabolism of the pharmacologically active N-desmethylclobazam. In CYP2C19 poor metabolizers, levels of N-desmethylclobazam were 5-fold higher in plasma and 2- to 3-fold higher in the urine than in CYP2C19 extensive metabolizers.23
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- Route of elimination
N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine. Following a single oral dose of radiolabeled drug, approximately 11% of the dose was excreted in the feces and approximately 82% was excreted in the urine.23
- Half-life
The estimated mean elimination half-lives (t½) of clobazam and N-desmethylclobazam were 36-42 hours and 71-82 hours, respectively.23
- Clearance
After a 20 to 40 mg/day administration of clobazam, the oral clearance is calculated to be 1.9 to 2.3 L/h.8
- Adverse Effects
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- Toxicity
Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.8) and Clinical Considerations]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association between benzodiazepines and major birth defects.23
Administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those expected at therapeutic doses in patients. Data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. ONFI should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Advise a pregnant woman and women of childbearing age of the potential risk to a fetus.23
Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to clobazam during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to clobazam during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.8)].23
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.23
Administration of clobazam to rats prior to and during mating and early gestation resulted in adverse effects on fertility and early embryonic development at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those in humans at the MRHD [see Nonclinical Toxicology (13.1)].23
In a study in which clobazam (0, 4, 36, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. The effect on bone density, but not on behavior, was reversible when the drug was discontinued. The no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (AUC) to clobazam and its major active metabolite, N-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients.23
In mice, oral administration of clobazam (0, 6, 12, or 24 mg/kg/day) for 2 years did not result in an increase in tumors. The highest dose tested was approximately 3 times the maximum recommended human dose (MRHD) of 40 mg/day, based on body surface area (mg/m2).23
In rats, oral administration of clobazam for 2 years resulted in increases in tumors of the thyroid gland (follicular cell adenoma and carcinoma) and liver (hepatocellular adenoma) at the mid and high doses. The low dose, not associated with an increase in tumors, was associated with plasma exposures (AUC) for clobazam and its major active metabolite, N-desmethylclobazam, less than that in humans at the MRHD.23
Clobazam and the major active metabolite, N-desmethylclobazam, were negative for genotoxicity, based on data from a battery of in vitro (bacteria reverse mutation, mammalian clastogenicity) and in vivo (mouse micronucleus) assays.23
In a fertility study in which clobazam (50, 350, or 750 mg/kg/day, corresponding to 12, 84, and 181 times the oral Maximum Recommended Human Dose, MRHD, of 40 mg/day based on mg/m2 body surface) was orally administered to male and female rats prior to and during mating and continuing in females to gestation day 6, increases in abnormal sperm and pre-implantation loss were observed at the highest dose tested. The no-effect level for fertility and early embryonic development in rats was associated with plasma exposures (AUC) for clobazam and its major active metabolite, N-desmethylclobazam, less than those in humans at the maximum recommended human dose of 40 mg/day.23
Clobazam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction.23
Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see Warnings and Precautions (5.2)].23
The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo.23
The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).23
The World Health Organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam.23
Clobazam may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening.23
Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see Warnings and Precautions (5.3)]. In clinical trials, cases of dependency were reported following the abrupt discontinuation of clobazam.23
Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g.,nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis,hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.23
Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used.23
Tolerance to clobazam may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effect of clobazam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.23
Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal [see Warnings and Precautions (5.2)]. Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raises the concern that additional drugs and/or alcohol are involved in the overdosage.23
In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway maintenance. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information.23
Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.23
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C19 CYP2C19*2 (A;A) / (A;G) G > A/C ADR Directly Studied Patients with this genotype have reduced metabolism of clobazam. Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of sedation, somnolence, and CNS depression can be increased when Clobazam is combined with 1,2-Benzodiazepine. Abacavir Clobazam may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Clobazam can be increased when it is combined with Abametapir. Abatacept The metabolism of Clobazam can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Clobazam. - Food Interactions
- Avoid alcohol. Alcohol increases clobazam absorption by 50%.
- Take with or without food. The absorption is unaffected by food.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Images
- International/Other Brands
- Aedon (Sanofi-Aventis) / Castilium (Sanofi-Aventis) / Clobam (Square) / Clobamax (Sherfarma) / Frisium (Sanofi-Aventis) / Grifoclobam (Chile) / Mystan (Dainippon Sumitomo) / Noiafren (Sanofi Aventis) / Sederlona / Urbanil (Sanofi-Aventis) / Urbanol (Sanofi-Aventis) / Urbanyl (Sanofi-Aventis) / Venium (Hudson)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Clobazam-10 Tablet 10 mg Oral Pro Doc Limitee 2003-12-09 2017-05-05 Canada Frisium Tab 10mg Tablet 10 mg / tab Oral Hoechst Canada Inc. 1991-12-31 1996-08-29 Canada Frisium Tablet 10mg Tablet 10 mg Oral Lundbeck Pharmaceuticals Llc 1997-03-24 2018-08-31 Canada Frisium Tablets 10mg Tablet 10 mg Oral Hoechst Roussel Canada Inc. 1994-12-31 1999-08-11 Canada Onfi Tablet 5 mg/1 Oral Lundbeck Inc. 2011-10-21 2011-10-31 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-clobazam Tablet 10 mg Oral Apotex Corporation 2001-11-28 Not applicable Canada Clobazam Tablet 20 mg/1 Oral CELLTRION USA, INC. 2021-01-21 Not applicable US Clobazam Suspension 2.5 mg/1mL Oral Amneal Pharmaceuticals NY LLC 2018-10-22 Not applicable US Clobazam Tablet 20 mg/1 Oral Upsher-Smith Laboratories, LLC 2018-10-22 Not applicable US Clobazam Tablet 10 mg/1 Oral Breckenridge Pharmaceutical, Inc. 2018-10-22 2025-07-31 US
Categories
- ATC Codes
- N05BA09 — Clobazam
- Drug Categories
- Anti-Anxiety Agents
- Anticonvulsants
- Benzazepines
- Benzodiazepines and benzodiazepine derivatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Agonists
- GABA-A Receptor Agonists
- Heterocyclic Compounds, Fused-Ring
- Nervous System
- Neurotransmitter Agents
- P-glycoprotein substrates
- Psycholeptics
- Psychotropic Drugs
- Tranquilizing Agents
- UGT1A4 Inhibitors
- UGT1A6 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzodiazepines
- Sub Class
- Not Available
- Direct Parent
- Benzodiazepines
- Alternative Parents
- 1,4-diazepines / Benzene and substituted derivatives / Aryl chlorides / 1,3-dicarbonyl compounds / Tertiary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides show 2 more
- Substituents
- 1,3-dicarbonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzodiazepine / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 13 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organochlorine compound, 1,4-benzodiazepinone (CHEBI:31413)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2MRO291B4U
- CAS number
- 22316-47-8
- InChI Key
- CXOXHMZGEKVPMT-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3
- IUPAC Name
- 7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione
- SMILES
- CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O
References
- Synthesis Reference
Hauptmann, K.H., Weber, K.-H., Zeile, K., Danneberg, P. and Giesemann, R.; South African Patent 68/0803; February 7,1968; assigned to Boehringer lngelheim GmbH, Germany.
- General References
- Freche C: [Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]. Sem Hop Ther. 1975 Apr;51(4):261-3. [Article]
- Authors unspecified: Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group. Epilepsia. 1991 May-Jun;32(3):407-16. [Article]
- Wildin JD, Pleuvry BJ, Mawer GE, Onon T, Millington L: Respiratory and sedative effects of clobazam and clonazepam in volunteers. Br J Clin Pharmacol. 1990 Feb;29(2):169-77. [Article]
- Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44. [Article]
- Giarratano M, Standley K, Benbadis SR: Clobazam for treatment of epilepsy. Expert Opin Pharmacother. 2012 Feb;13(2):227-33. doi: 10.1517/14656566.2012.647686. Epub 2012 Jan 13. [Article]
- Yang LP, Scott LJ: Clobazam : in patients with Lennox-Gastaut syndrome. CNS Drugs. 2012 Nov;26(11):983-91. doi: 10.1007/s40263-012-0007-0. [Article]
- Walzer M, Bekersky I, Blum RA, Tolbert D: Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012 Apr;32(4):340-53. doi: 10.1002/j.1875-9114.2012.01028.x. Epub 2012 Mar 15. [Article]
- Tolbert D, Larsen F: A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019 Jan;59(1):7-19. doi: 10.1002/jcph.1313. Epub 2018 Oct 4. [Article]
- Gauthier AC, Mattson RH: Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy. CNS Neurosci Ther. 2015 Jul;21(7):543-8. doi: 10.1111/cns.12399. Epub 2015 Apr 28. [Article]
- Jensen HS, Nichol K, Lee D, Ebert B: Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for alpha(2)- versus alpha(1)-GABA(A)-receptor complexes. PLoS One. 2014 Feb 12;9(2):e88456. doi: 10.1371/journal.pone.0088456. eCollection 2014. [Article]
- Nakamura F, Suzuki S, Nishimura S, Yagi K, Seino M: Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture. Epilepsia. 1996 Aug;37(8):728-35. doi: 10.1111/j.1528-1157.1996.tb00643.x. [Article]
- Stafstrom CE, Carmant L: Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015 Jun 1;5(6):a022426. doi: 10.1101/cshperspect.a022426. [Article]
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Guerreiro CA: Clobazam: the phoenix drug (from the very old to the brand new). Indian J Med Res. 2014 Aug;140(2):163-4. [Article]
- Sankar R: GABA(A) receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs. 2012 Mar 1;26(3):229-44. doi: 10.2165/11599020-000000000-00000. [Article]
- Pernea M, Sutcliffe AG: Clobazam and Its Use in Epilepsy. Pediatr Rep. 2016 Jun 15;8(2):6516. doi: 10.4081/pr.2016.6516. eCollection 2016 Jun 15. [Article]
- Faulkner MA: Comprehensive overview: efficacy, tolerability, and cost-effectiveness of clobazam in Lennox-Gastaut syndrome. Ther Clin Risk Manag. 2015 Jun 8;11:905-14. doi: 10.2147/TCRM.S55930. eCollection 2015. [Article]
- Humayun MJ, Samanta D, Carson RP: Clobazam. . [Article]
- Tanabe T, Awaya Y, Matsuishi T, Iyoda K, Nagai T, Kurihara M, Yamamoto K, Minagawa K, Maekawa K: Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)--a nationwide questionnaire survey in Japan. Brain Dev. 2008 Nov;30(10):629-35. doi: 10.1016/j.braindev.2008.03.002. [Article]
- Sivakumar S, Ibrahim M, Parker D Jr, Norris G, Shah A, Mohamed W: Clobazam: An effective add-on therapy in refractory status epilepticus. Epilepsia. 2015 Jun;56(6):e83-9. doi: 10.1111/epi.13013. Epub 2015 May 12. [Article]
- Feely M, Calvert R, Gibson J: Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Lancet. 1982 Jul 10;2(8289):71-3. doi: 10.1016/s0140-6736(82)91691-9. [Article]
- Rickels K, Brown AS, Cohen D, Harris H, Hurowitz A, Lindenbaum EJ, Ross HA, Weinstock R, Wiseman K, Zal M: Clobazam and diazepam in anxiety. Clin Pharmacol Ther. 1981 Jul;30(1):95-100. doi: 10.1038/clpt.1981.132. [Article]
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
- DailyMed Label: ONFI (clobazam) oral suspension or tablets, CIV [Link]
- Clobazam MSDS LGC [Link]
- Clobazam (T3D4564) [Link]
- Health Canada Approved Drug Proucts: APO-CLOBAZAM (Clobazam) tablets, for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0014493
- KEGG Drug
- D01253
- PubChem Compound
- 2789
- PubChem Substance
- 46506115
- ChemSpider
- 2687
- BindingDB
- 50247888
- 21241
- ChEBI
- 31413
- ChEMBL
- CHEMBL70418
- ZINC
- ZINC000000001175
- Therapeutic Targets Database
- DAP000672
- PharmGKB
- PA10888
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Clobazam
- FDA label
- Download (595 KB)
- MSDS
- Download (57.5 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Anxiety / Epilepsy 1 4 Recruiting Treatment Drug-resistant Epilepsy 1 4 Unknown Status Treatment Epilepsy 2 4 Unknown Status Treatment Refractory Epilepsy 1 3 Completed Basic Science Back Pain Lower Back 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Oral 2.5 mg/1mL Suspension Oral 2.5 mg/1mL Suspension Oral 1 mg/ml Suspension Oral 2 mg/ml Capsule Tablet Oral 10.00 mg Tablet Oral Tablet Oral 20 mg Tablet Oral 10 mg / tab Tablet Oral 10 mg Tablet Oral 1000000 mg Tablet Oral 2000000 mg Tablet Oral 10 mg/1 Tablet Oral 20 mg/1 Tablet Oral 5 mg/1 Film Oral 10 mg/1 Film Oral 20 mg/1 Film Oral 5 mg/1 Suspension Oral 0.25 g - Prices
Unit description Cost Unit Apo-Clobazam 10 mg Tablet 0.23USD tablet Novo-Clobazam 10 mg Tablet 0.23USD tablet Pms-Clobazam 10 mg Tablet 0.23USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8603514 No 2013-12-10 2024-04-03 US US8765167 No 2014-07-01 2024-02-20 US US11541002 No 2019-09-05 2039-09-05 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 182-185ºC L44888 water solubility 188 mg/L L44983 logP 2.12 HENCZI,M ET AL. (1995),L44973 - Predicted Properties
Property Value Source Water Solubility 0.164 mg/mL ALOGPS logP 2.14 ALOGPS logP 2.55 Chemaxon logS -3.3 ALOGPS pKa (Strongest Acidic) 5.82 Chemaxon pKa (Strongest Basic) -6.7 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 40.62 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 80.3 m3·mol-1 Chemaxon Polarizability 30.07 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.99 Blood Brain Barrier + 0.9904 Caco-2 permeable + 0.7487 P-glycoprotein substrate Non-substrate 0.5733 P-glycoprotein inhibitor I Non-inhibitor 0.5462 P-glycoprotein inhibitor II Non-inhibitor 0.9204 Renal organic cation transporter Non-inhibitor 0.7373 CYP450 2C9 substrate Non-substrate 0.7058 CYP450 2D6 substrate Non-substrate 0.8607 CYP450 3A4 substrate Substrate 0.6871 CYP450 1A2 substrate Non-inhibitor 0.6829 CYP450 2C9 inhibitor Non-inhibitor 0.5296 CYP450 2D6 inhibitor Non-inhibitor 0.8908 CYP450 2C19 inhibitor Non-inhibitor 0.5791 CYP450 3A4 inhibitor Inhibitor 0.7008 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5308 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.7846 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.7313 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9896 hERG inhibition (predictor II) Non-inhibitor 0.8651
Spectra
- Mass Spec (NIST)
- Download (11.4 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 168.6874803 predictedDarkChem Lite v0.1.0 [M-H]- 164.7596 predictedDeepCCS 1.0 (2019) [M+H]+ 169.4000803 predictedDarkChem Lite v0.1.0 [M+H]+ 167.11758 predictedDeepCCS 1.0 (2019) [M+Na]+ 169.0764803 predictedDarkChem Lite v0.1.0 [M+Na]+ 173.21074 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- Curator comments
- The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Components:
References
- Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [Article]
- Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- Curator comments
- Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
- General Function
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Components:
References
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Tolbert D, Larsen F: A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019 Jan;59(1):7-19. doi: 10.1002/jcph.1313. Epub 2018 Oct 4. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Huddart R, Leeder JS, Altman RB, Klein TE: PharmGKB summary: clobazam pathway, pharmacokinetics. Pharmacogenet Genomics. 2018 Apr;28(4):110-115. doi: 10.1097/FPC.0000000000000327. [Article]
- Walzer M, Bekersky I, Blum RA, Tolbert D: Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012 Apr;32(4):340-53. doi: 10.1002/j.1875-9114.2012.01028.x. Epub 2012 Mar 15. [Article]
- Tolbert D, Bekersky I, Chu HM, Ette EI: Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions. J Clin Pharmacol. 2016 Mar;56(3):365-74. doi: 10.1002/jcph.603. Epub 2015 Sep 29. [Article]
- Flockhart Table of Drug Interactions [Link]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C18
- Uniprot ID
- P33260
- Uniprot Name
- Cytochrome P450 2C18
- Molecular Weight
- 55710.075 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- de Leon J, Spina E, Diaz FJ: Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013 Feb;35(1):30-47. doi: 10.1097/FTD.0b013e31827ada88. [Article]
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- de Leon J, Spina E, Diaz FJ: Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies. Ther Drug Monit. 2013 Feb;35(1):30-47. doi: 10.1097/FTD.0b013e31827ada88. [Article]
- Huddart R, Leeder JS, Altman RB, Klein TE: PharmGKB summary: clobazam pathway, pharmacokinetics. Pharmacogenet Genomics. 2018 Apr;28(4):110-115. doi: 10.1097/FPC.0000000000000327. [Article]
- Clobazam FDA label [Link]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
References
- Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Upregulator
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Protein homodimerization activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1-4
- Molecular Weight
- 60024.535 Da
References
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Protein homodimerization activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks trans...
- Gene Name
- UGT1A6
- Uniprot ID
- P19224
- Uniprot Name
- UDP-glucuronosyltransferase 1-6
- Molecular Weight
- 60750.215 Da
References
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
- Gene Name
- UGT2B4
- Uniprot ID
- P06133
- Uniprot Name
- UDP-glucuronosyltransferase 2B4
- Molecular Weight
- 60512.035 Da
References
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Patsalos PN, Zugman M, Lake C, James A, Ratnaraj N, Sander JW: Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations. Epilepsia. 2017 Jul;58(7):1234-1243. doi: 10.1111/epi.13802. Epub 2017 May 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Patsalos PN, Zugman M, Lake C, James A, Ratnaraj N, Sander JW: Serum protein binding of 25 antiepileptic drugs in a routine clinical setting: A comparison of free non-protein-bound concentrations. Epilepsia. 2017 Jul;58(7):1234-1243. doi: 10.1111/epi.13802. Epub 2017 May 24. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55