Identification
- Summary
Saquinavir is an HIV protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 with advanced immunodeficiency.
- Brand Names
- Invirase
- Generic Name
- Saquinavir
- DrugBank Accession Number
- DB01232
- Background
Saquinavir is an HIV-1 protease inhibitor used in combination with ritonavir and other antiretrovirals for the treatment of human immunodeficiency virus-1 (HIV-1) infection. In 1995 it became the first protease inhibitor approved by the FDA, followed shortly by ritonavir in 1996, and remains in clinical use today due to a relatively benign adverse effect profile as compared to other antiretroviral therapies.2 While its efficacy was initially limited by exceptionally poor oral bioavailability (approximately 4%),6 its current indications require the co-administration of ritonavir - a potent enzyme inhibitor - that increases the bioavailability and subsequent serum concentrations of saquinavir, thus dramatically improving antiviral activity.2,6,7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Saquinavir (DB01232)
- Weight
- Average: 670.8408
Monoisotopic: 670.38426874 - Chemical Formula
- C38H50N6O5
- Synonyms
- Saquinavir
- External IDs
- Ro 31 8959
- Ro 31-8959
- RO 31-8959/000
- Ro 318959
- RO-31-8959/000
- Sch 52852
- SCH-52852
Pharmacology
- Indication
Saquinavir is indicated, in combination with ritonavir and other antiretroviral agents, for the treatment of HIV-1 infection in patients 16 years of age and older.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hiv-1 infection Regimen in combination with: Ritonavir (DB00503) •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Saquinavir exerts its antiviral activity by inhibiting an enzyme critical for the HIV-1 viral lifecycle.6 Like other protease inhibitors, saquinavir has a propensity for participating in drug interactions - use caution when administering saquinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common.6 Saquinavir is known to increase the QTc-interval in otherwise healthy individuals, and should therefore be used with caution in patients maintained on other QTc-prolonging medications or for whom prolongation of the QTc-interval may be of particular consequence (e.g. patients with pre-existing heart disease).6 Careful and regular monitoring of patient bloodwork is recommended, as saquinavir has been associated with the development of metabolic complications (e.g. diabetes mellitus, hyperlipidemia) and worsening of pre-existing liver disease.6
- Mechanism of action
The HIV lifecycle is comprised of 3 distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious.4 At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV-1 protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle.4
Saquinavir is an inhibitor of the HIV-1 protease enzyme.6 Its design is based on the "peptidomimetic" principle, wherein the molecule contains a hydroxyethylene scaffold that mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved.5 By preventing HIV-1 protease activity, and thus the proteolysis of the Gag polyprotein, saquinavir results in the production of immature, non-infectious viral particles.
Target Actions Organism AHuman immunodeficiency virus type 1 protease inhibitorHuman immunodeficiency virus 1 - Absorption
The absolute bioavailability of orally administered saquinavir is only ~4%,6 thought to be a consequence of incomplete absorption and extensive first-pass metabolism. It is co-administered with ritonavir, another protease inhibitor and a potent inhibitor of the enzymes responsible for saquinavir's first-pass metabolism, in order to dramatically boost its serum concentrations and, by extension, its therapeutic efficacy. Following administration of saquinavir 1000mg twice daily with ritonavir 100mg twice daily the AUC24h at steady-state was 39026 ng.h/mL.6
- Volume of distribution
The steady-state volume of distribution of saquinavir is approximately 700 L, suggesting extensive distribution into tissues.6
- Protein binding
Saquinavir is approximately 98% plasma protein-bound independent of serum concentration.6
- Metabolism
Saquinavir is extensively metabolized in the liver following oral administration, and in vitro studies have shown that >90% of its biotransformation is mediated by the CYP3A4 isoenzyme. Saquinavir is rapidly metabolized to a number of inactive mono- and di-hydroxylated compounds.6
Hover over products below to view reaction partners
- Route of elimination
The primary means of elimination of saquinavir appears to be extensive hepatic metabolism followed by fecal excretion of both the parent drug and metabolic products.6 Following the administration of radiolabeled saquinavir (both orally and intravenously), approximately 81-88% of radioactivity is recovered in the feces within 5 days of dosing while only 1-3% is recovered in the urine. Mass balance studies indicate that only 13% of orally-administered plasma radioactivity is attributed to unchanged parent drug, with the remainder comprising metabolic products of saquinavir's hepatic metabolism. In contrast, intravenous administration resulted in approximately 66% of the circulating plasma radioactivity being attributed to unchanged parent drug, suggesting a high degree of first-pass metabolism with oral administration.6
- Half-life
Not Available
- Clearance
The systemic clearance of saquinavir is approximately 1.14 L/h/kg following intravenous administration.6
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The oral LD50 of saquinavir in both rats and mice is >5 g/kg.8 Data regarding overdose with saquinavir are limited.6 No acute toxicities or sequelae were noted in a patient ingesting 8 grams of saquinavir as a single dose, and a second subject ingesting 2.4 grams as a single dose experienced throat pain that lasted for 6 hours and subsequently resolved.6 Treatment of overdose should consist of symptomatic and supportive measures. Dialysis is unlikely to be of benefit given saquinavir's extensive protein-binding.6
- 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);">
- Not Available
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 metabolism of 1,2-Benzodiazepine can be decreased when combined with Saquinavir. Abametapir The serum concentration of Saquinavir can be increased when it is combined with Abametapir. Abatacept The metabolism of Saquinavir can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Saquinavir. Abiraterone The metabolism of Abiraterone can be decreased when combined with Saquinavir. - Food Interactions
- Avoid grapefruit products. Co-administration with grapefruit-containing products inhibits the metabolism of saquinavir.
- Take after a meal.
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 Ingredients
Ingredient UNII CAS InChI Key Saquinavir mesylate UHB9Z3841A 149845-06-7 IRHXGOXEBNJUSN-YOXDLBRISA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fortovase Capsule, liquid filled 200 mg/1 Oral Genentech, Inc. 1997-11-07 2012-04-18 US 
Fortovase Roche Capsule 200 mg Oral Hoffmann La Roche 1998-11-26 2007-03-06 Canada 
Invirase Tablet 500 mg Oral Hoffmann La Roche 2006-04-10 2021-01-06 Canada Invirase Tablet, film coated 500 mg/1 Oral Genentech, Inc. 2004-12-17 2024-04-30 US Invirase Tablet, film coated 500 mg/1 Oral State of Florida DOH Central Pharmacy 2009-07-01 Not applicable US
Categories
- ATC Codes
- J05AE01 — Saquinavir
- Drug Categories
- Agents Causing Muscle Toxicity
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- BCRP/ABCG2 Inhibitors
- BSEP/ABCB11 Substrates
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A5 Inhibitors (strong)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Inhibitors
- Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A7 Inhibitors (strong)
- Cytochrome P-450 CYP3A7 Inhibitors (weak)
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- HIV Protease Inhibitors
- Hyperglycemia-Associated Agents
- Isoquinolines
- Moderate Risk QTc-Prolonging Agents
- OATP1B1/SLCO1B1 Inhibitors
- OCT1 inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Protease Inhibitors
- QTc Prolonging Agents
- Quinolines
- Viral Protease Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinoline carboxamides. These are quinolines in which the quinoline ring system is substituted by one or more carboxamide groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Quinoline carboxamides
- Direct Parent
- Quinoline carboxamides
- Alternative Parents
- Phenylbutylamines / Amphetamines and derivatives / Pyridinecarboxylic acids and derivatives / Piperidinecarboxamides / 2-heteroaryl carboxamides / Aralkylamines / Heteroaromatic compounds / Trialkylamines / Secondary carboxylic acid amides / Secondary alcohols show 8 more
- Substituents
- 1,2-aminoalcohol / 2-heteroaryl carboxamide / 2-piperidinecarboxamide / Alcohol / Amine / Amino acid or derivatives / Amphetamine or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle show 26 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- quinolines, L-asparagine derivative (CHEBI:63621)
- Affected organisms
- Human Immunodeficiency Virus
Chemical Identifiers
- UNII
- L3JE09KZ2F
- CAS number
- 127779-20-8
- InChI Key
- QWAXKHKRTORLEM-UGJKXSETSA-N
- InChI
- InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1
- IUPAC Name
- (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide
- SMILES
- [H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)C1=NC3=C(C=CC=C3)C=C1)[C@@H](C2)C(=O)NC(C)(C)C
References
- Synthesis Reference
- US5196438
- General References
- Forestier F, de Renty P, Peytavin G, Dohin E, Farinotti R, Mandelbrot L: Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model. Am J Obstet Gynecol. 2001 Jul;185(1):178-81. [Article]
- De Clercq E: The history of antiretrovirals: key discoveries over the past 25 years. Rev Med Virol. 2009 Sep;19(5):287-99. doi: 10.1002/rmv.624. [Article]
- Kupferschmidt HH, Fattinger KE, Ha HR, Follath F, Krahenbuhl S: Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br J Clin Pharmacol. 1998 Apr;45(4):355-9. doi: 10.1046/j.1365-2125.1998.t01-1-00687.x. [Article]
- Sundquist WI, Krausslich HG: HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006924. doi: 10.1101/cshperspect.a006924. [Article]
- De Clercq E: Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20. doi: 10.1016/j.ijantimicag.2008.10.010. Epub 2008 Dec 23. [Article]
- FDA Approved Drug Products: Invirase (saquinavir mesylate) oral tablets [Link]
- Health Canada Product Monograph: Invirase (saquinavir mesylate) for oral administration [Link]
- CaymanChem: Saquinavir MSDS [Link]
- External Links
- KEGG Drug
- D00429
- PubChem Compound
- 441243
- PubChem Substance
- 46508726
- ChemSpider
- 390016
- BindingDB
- 519
- 83395
- ChEBI
- 63621
- ChEMBL
- CHEMBL114
- ZINC
- ZINC000003914596
- Therapeutic Targets Database
- DAP000171
- PharmGKB
- PA451305
- PDBe Ligand
- ROC
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Saquinavir
- PDB Entries
- 1c6z / 1fb7 / 1hxb / 2nmy / 2nmz / 2nnk / 2nnp / 3cyx / 3d1x / 3d1y … show 18 more
- FDA label
- Download (362 KB)
- MSDS
- Download (15.8 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 Diagnostic Cardiovascular Disease (CVD) / HIV Lipodystrophy Syndrome 1 4 Completed Prevention Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Healthy Subjects (HS) / Human Immunodeficiency Virus (HIV) Infections 1 4 Completed Treatment Human Immunodeficiency Virus (HIV) Infections 6 3 Completed Not Available Directly Observed Therapy / Human Immunodeficiency Virus (HIV) Infections 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- A-S Medication Solutions LLC
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- R.P. Scherer GmbH and Co. KG
- Dosage Forms
Form Route Strength Capsule, coated Oral 200 mg Capsule Oral Capsule, liquid filled Oral 200 mg/1 Capsule Oral 200 mg Tablet Oral 500.0000 mg Capsule Oral 200 mg/1 Tablet Oral 500 mg Tablet, film coated Oral 500 mg/1 Tablet, film coated Oral 500 MG Tablet Oral 500.000 mg Tablet, coated Oral 500 mg Tablet, film coated Oral - Prices
Unit description Cost Unit Invirase 500 mg tablet 8.72USD tablet Invirase 200 mg capsule 3.87USD capsule Fortovase 200 mg capsule 1.46USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5196438 No 1993-03-23 2010-11-19 US CA2224125 No 2004-09-28 2016-06-04 Canada CA2030433 No 1997-10-21 2010-11-21 Canada US6352717 Yes 2002-03-05 2020-05-16 US US6008228 Yes 1999-12-28 2015-12-06 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 349.84 °C Not Available water solubility Insoluble Not Available logP 3.8 Not Available Caco2 permeability -6.26 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.00247 mg/mL ALOGPS logP 4.04 ALOGPS logP 3.16 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 13.61 Chemaxon pKa (Strongest Basic) 8.47 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 166.75 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 186.67 m3·mol-1 Chemaxon Polarizability 73.76 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.7774 Blood Brain Barrier - 0.9949 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.9048 P-glycoprotein inhibitor I Inhibitor 0.8563 P-glycoprotein inhibitor II Inhibitor 0.5195 Renal organic cation transporter Non-inhibitor 0.8612 CYP450 2C9 substrate Non-substrate 0.8593 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.7406 CYP450 1A2 substrate Non-inhibitor 0.8729 CYP450 2C9 inhibitor Non-inhibitor 0.7442 CYP450 2D6 inhibitor Non-inhibitor 0.8536 CYP450 2C19 inhibitor Non-inhibitor 0.7124 CYP450 3A4 inhibitor Inhibitor 0.5219 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9053 Ames test Non AMES toxic 0.8489 Carcinogenicity Non-carcinogens 0.865 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6007 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9687 hERG inhibition (predictor II) Inhibitor 0.8153
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 260.6761256 predictedDarkChem Lite v0.1.0 [M-H]- 234.3534 predictedDeepCCS 1.0 (2019) [M+H]+ 259.1169256 predictedDarkChem Lite v0.1.0 [M+H]+ 236.2488 predictedDeepCCS 1.0 (2019) [M+Na]+ 259.4357256 predictedDarkChem Lite v0.1.0 [M+Na]+ 242.13132 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Aspartic-type endopeptidase activity
- Specific Function
- Not Available
- Gene Name
- pol
- Uniprot ID
- Q72874
- Uniprot Name
- Pol polyprotein
- Molecular Weight
- 10778.7 Da
References
- Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [Article]
- Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. Epub 2007 Jul 16. [Article]
- Dandache S, Coburn CA, Oliveira M, Allison TJ, Holloway MK, Wu JJ, Stranix BR, Panchal C, Wainberg MA, Vacca JP: PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63. doi: 10.1002/jmv.21329. [Article]
- Rhee SY, Taylor J, Fessel WJ, Kaufman D, Towner W, Troia P, Ruane P, Hellinger J, Shirvani V, Zolopa A, Shafer RW: HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother. 2010 Oct;54(10):4253-61. doi: 10.1128/AAC.00574-10. Epub 2010 Jul 26. [Article]
- Alcaro S, Artese A, Ceccherini-Silberstein F, Ortuso F, Perno CF, Sing T, Svicher V: Molecular dynamics and free energy studies on the wild-type and mutated HIV-1 protease complexed with four approved drugs: mechanism of binding and drug resistance. J Chem Inf Model. 2009 Jul;49(7):1751-61. doi: 10.1021/ci900012k. [Article]
- Vella S, Lazzarin A, Carosi G, Sinicco A, Armignacco O, Angarano G, Andreoni M, Tambussi G, Chiodera A, Floridia M, Scaccabarozzi S, Facey K, Duncan I, Boudes P, Bragman K: A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection. Antivir Ther. 1996 Aug;1(3):129-40. [Article]
- Hoetelmans RM, Meenhorst PL, Mulder JW, Burger DM, Koks CH, Beijnen JH: Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir. Pharm World Sci. 1997 Aug;19(4):159-75. [Article]
- FDA Approved Drug Products: Invirase (saquinavir mesylate) oral tablets [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
- Parikh S, Ouedraogo JB, Goldstein JA, Rosenthal PJ, Kroetz DL: Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther. 2007 Aug;82(2):197-203. doi: 10.1038/sj.clpt.6100122. Epub 2007 Mar 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9. doi: 10.1021/js980197h. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [Article]
- Eagling VA, Wiltshire H, Whitcombe IW, Back DJ: CYP3A4-mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in vitro. Xenobiotica. 2002 Jan;32(1):1-17. doi: 10.1080/00498250110085845. [Article]
- Schmitt C, Hofmann C, Riek M, Patel A, Zwanziger E: Effect of saquinavir-ritonavir on cytochrome P450 3A4 activity in healthy volunteers using midazolam as a probe. Pharmacotherapy. 2009 Oct;29(10):1175-81. doi: 10.1592/phco.29.10.1175. [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
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [Article]
- Frohlich M, Hoffmann MM, Burhenne J, Mikus G, Weiss J, Haefeli WE: Association of the CYP3A5 A6986G (CYP3A5*3) polymorphism with saquinavir pharmacokinetics. Br J Clin Pharmacol. 2004 Oct;58(4):443-4. doi: 10.1111/j.1365-2125.2004.02159.x. [Article]
- Josephson F, Allqvist A, Janabi M, Sayi J, Aklillu E, Jande M, Mahindi M, Burhenne J, Bottiger Y, Gustafsson LL, Haefeli WE, Bertilsson L: CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir. Clin Pharmacol Ther. 2007 May;81(5):708-12. doi: 10.1038/sj.clpt.6100117. Epub 2007 Feb 28. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [Article]
- Flockhart Table of Drug Interactions [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
- Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. [Article]
- Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [Article]
- Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
- Kim AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45. [Article]
- Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH: P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol. 2001 Apr;59(4):806-13. [Article]
- Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [Article]
- Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. [Article]
- Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active organic cation transmembrane transporter activity
- Specific Function
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Zhang L, Gorset W, Washington CB, Blaschke TF, Kroetz DL, Giacomini KM: Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Drug Metab Dispos. 2000 Mar;28(3):329-34. [Article]
- Moss DM, Liptrott NJ, Siccardi M, Owen A: Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter. Front Pharmacol. 2015 Apr 10;6:78. doi: 10.3389/fphar.2015.00078. eCollection 2015. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
- Gene Name
- SLCO1A2
- Uniprot ID
- P46721
- Uniprot Name
- Solute carrier organic anion transporter family member 1A2
- Molecular Weight
- 74144.105 Da
References
- Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2004 Jul;310(1):334-41. Epub 2004 Mar 8. [Article]
- Janneh O, Owen A, Chandler B, Hartkoorn RC, Hart CA, Bray PG, Ward SA, Back DJ, Khoo SH: Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS. 2005 Dec 2;19(18):2097-102. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Transporter activity
- Specific Function
- Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
- Gene Name
- ABCC1
- Uniprot ID
- P33527
- Uniprot Name
- Multidrug resistance-associated protein 1
- Molecular Weight
- 171589.5 Da
References
- Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [Article]
- Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, Schinkel AH: Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS. 2002 Nov 22;16(17):2295-301. [Article]
- Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JH, Schinkel AH, Borst P: Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem. 2003 Jun 27;278(26):23538-44. Epub 2003 Apr 17. [Article]
- Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76709.98 Da
References
- Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Transporter activity
- Specific Function
- Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
- Gene Name
- ABCB11
- Uniprot ID
- O95342
- Uniprot Name
- Bile salt export pump
- Molecular Weight
- 146405.83 Da
References
- Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54