Identification
- Summary
Tixocortol is a corticosteroid used for the symptomatic treatment of rhinitis, pharyngitis, and ulcerative colitis.
- Generic Name
- Tixocortol
- DrugBank Accession Number
- DB09091
- Background
Tixocortol is a 21-thiol derivative of hydrocortisone classified as a class A corticosteroid. It is a synthetic steroid with topical anti-inflammatory properties without the systemic glucocorticoid and mineralocorticoid activities and toxicity.11
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Structure
Structure for Tixocortol (DB09091)
- Weight
- Average: 378.53
Monoisotopic: 378.18648062 - Chemical Formula
- C21H30O4S
- Synonyms
- Tixocortol
Pharmacology
- Indication
Tixocortol is indicated for the treatment of rhinitis as a nasal suspension or aerosol. It is also used in the form of lozenges for the treatment of pharyngitis and in the form of enemas or rectal solution for the treatment of ulcerative colitis. Tixocortol can be used orally in a suspension or powder for the treatment of inflammatory conditions.10 It is also the substance used for the screening of contact allergies to class A steroids.2
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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
Tixocortol presents the characteristic of local action which reduces significantly the side effects of systemic glucocorticoids. Reports have demonstrated that gastrointestinal administration of tixocortol generates a decrease in abdominal pain, bleeding, and frequency of stools which resulted in an amelioration in the malabsorption laboratory tests. All the effects were independent of suppression of the pituitary-adrenal axis, which was shown by the absence of significant depression of cortisol.1 Administration of tixocortol as a nasal spray has been shown to respect nasal drainage by the ciliary beats of the pituitary mucosa.3 The actions of tixocortol have no effect on leukocyte count, blood glucose level, sodium urinary excretion, and immunosupressive activity on lymphocytes.9
- Mechanism of action
The mechanism of action of tixocortol is similar to other corticosteroids regarding the binding sites and prostaglandin synthesis but the local properties of tixocortol are given by the immediate liver metabolism and transformation withing red blood cells. All the immediate transformations of tixocortol classified it as part of the nonsystemic steroids.11
Target Actions Organism AGlucocorticoid receptor binderHumans AHistone deacetylase 2 stimulatorHumans - Absorption
The absorption of tixocortol is the same as in other steroids including hydrocortisone.11 Oral administration of tixocortol presents a 10-20% bioavailability with a significantly lower plasma Cmax than cortisol. The fast metabolism, larger volume of distribution and low bioavailability donates tixocortol with the absence of systemic activity.4
- Volume of distribution
Studies have shown that oral or intravenous administration of tixocortol presents a significantly larger volume of distribution compared to cortisol of 21.7 L/kg.4
- Protein binding
The presence of the C-17 in the corticosteroids is a protein binding site.8
- Metabolism
Tixocortol is rapidly modified within red blood cells and it is immediately metabolized by a first-pass liver metabolism.11 The metabolites of tixocortol are mainly represented by the formation of sulfo- and glucurono-conjugates which are later hydrolyzed from the conjugate forming neutral steroids. The metabolic transformations are the reduction of the 3-keto and delta 4 system, reduction of the C-20 carbonyl group, oxidation of the C-11 alcohol and cleavage of the side chain at C-17. The specific metabolic pathways of the C-21 thiol ester function were its transformation into methylthio, methylsulfonyl and methylsulfonyl derivatives and reductive cleavage of the C-21-S bond leading to 21-methyl structures. None of the metabolites have affinity for glucocorticoid receptors. This and the extensive metabolism explains the exclusive local activities of tixocortol.5
- Route of elimination
Tixocortol has a rapid elimination after continuous metabolism. Urine analysis of oral administration of tixocortol demonstrate a complete lack of unchanged drug.5
- Half-life
Tixocortol presents a shorter half-life than cortisol.6
- Clearance
Studies have shown that oral or intravenous administration of tixocortol presents a significantly larger clearance rate compared to cortisol of 33.3 L h/kg.4
- Adverse Effects
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Diverse studies performed on tixocortol proved that this drug is non-toxic and non-immunosupressive. This low toxicity and abscence of immuno supression gave tixocortol the potential to be a lead for topical or local anti-inflammatory treatments.7 Nevertheless, toxicortol is a potent cutaneous sensitizer, causing a local allergy.3
- 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 softwareAbacavir Abacavir may decrease the excretion rate of Tixocortol which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Tixocortol. Acarbose The risk or severity of hyperglycemia can be increased when Tixocortol is combined with Acarbose. Aceclofenac The risk or severity of gastrointestinal irritation can be increased when Tixocortol is combined with Aceclofenac. Acemetacin The risk or severity of gastrointestinal irritation can be increased when Tixocortol is combined with Acemetacin. - Food Interactions
- No interactions found.
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 Tixocortol pivalate 6K28E35M3B 55560-96-8 BISFDZNIUZIKJD-XDANTLIUSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Rectovalone 250mg/100ml Suspension 250 mg / 100 mL Rectal Axcan Pharma 1991-12-31 1998-07-16 Canada 
- Mixture Products
Categories
- ATC Codes
- R01AD57 — Tixocortol, combinations
- R01AD — Corticosteroids
- R01A — DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE
- R01 — NASAL PREPARATIONS
- R — RESPIRATORY SYSTEM
- R01AD — Corticosteroids
- R01A — DECONGESTANTS AND OTHER NASAL PREPARATIONS FOR TOPICAL USE
- R01 — NASAL PREPARATIONS
- R — RESPIRATORY SYSTEM
- Drug Categories
- 11-Hydroxycorticosteroids
- 17-Hydroxycorticosteroids
- Adrenal Cortex Hormones
- Alimentary Tract and Metabolism
- Anti-Allergic Agents
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Cell-mediated Immunity
- Corticosteroids
- Corticosteroids Acting Locally
- Drugs that are Mainly Renally Excreted
- Fused-Ring Compounds
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hydroxycorticosteroids
- Immunosuppressive Agents
- Increased Histamine Release
- Intestinal Antiinflammatory Agents
- Nasal Preparations
- Pregnanes
- Pregnenediones
- Pregnenes
- Standardized Chemical Allergen
- Steroids
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Pregnane steroids
- Direct Parent
- Gluco/mineralocorticoids, progestogins and derivatives
- Alternative Parents
- 20-oxosteroids / 3-oxo delta-4-steroids / 17-hydroxysteroids / 11-beta-hydroxysteroids / Delta-4-steroids / Cyclohexenones / Tertiary alcohols / Alpha-hydroxy ketones / Secondary alcohols / Cyclic alcohols and derivatives show 3 more
- Substituents
- 11-beta-hydroxysteroid / 11-hydroxysteroid / 17-hydroxysteroid / 20-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Alcohol / Aliphatic homopolycyclic compound / Alkylthiol / Alpha-hydroxy ketone show 16 more
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- 3-oxo steroid, 11beta-hydroxy steroid, 17alpha-hydroxy steroid, 20-oxo steroid, steroid sulfide (CHEBI:63560)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- ZX3KEK657Z
- CAS number
- 61951-99-3
- InChI Key
- YWDBSCORAARPPF-VWUMJDOOSA-N
- InChI
- InChI=1S/C21H30O4S/c1-19-7-5-13(22)9-12(19)3-4-14-15-6-8-21(25,17(24)11-26)20(15,2)10-16(23)18(14)19/h9,14-16,18,23,25-26H,3-8,10-11H2,1-2H3/t14-,15-,16-,18+,19-,20-,21-/m0/s1
- IUPAC Name
- (1S,2R,10S,11S,14R,15S,17S)-14,17-dihydroxy-2,15-dimethyl-14-(2-sulfanylacetyl)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-5-one
- SMILES
- [H][C@@]12CC[C@](O)(C(=O)CS)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
References
- General References
- Friedman BS, Metcalfe DD: Effects of tixocortol pivalate on gastrointestinal disease in systemic mastocytosis: a preliminary study. Clin Exp Allergy. 1991 Mar;21(2):183-8. [Article]
- Rasanen L, Tuomi ML, Ylitalo L: Reactivity of tixocortol pivalate-positive patients in intradermal and oral provocation tests. Br J Dermatol. 1996 Dec;135(6):931-4. [Article]
- Bircher AJ, Hirsbrunner P, Tschopp K, Wildermuth V: Allergic contact dermatitis from tixocortol pivalate in a nasal spray masquerading as infectious complication of sinusitis. ORL J Otorhinolaryngol Relat Spec. 1995 Jan-Feb;57(1):54-6. [Article]
- Chanoine F, Junien JL: Comparative pharmacokinetic studies of tixocortol pivalate and cortisol in the rat. J Steroid Biochem. 1984 Oct;21(4):453-9. [Article]
- Chanoine F, Grenot C, Sellier N, Barrett WE, Thompson RM, Fentiman AF, Nixon JR, Goyer R, Junien JL: Isolation and identification of major metabolites of tixocortol pivalate in human urine. Drug Metab Dispos. 1987 Nov-Dec;15(6):868-76. [Article]
- Lelievre V, Bertin B, Chanoine F, Bure J, Junien JL: Correlation between binding activity, inhibition of lymphoblastic transformation and metabolism of tixocortol 21 pivalate in mouse thymocytes. Agents Actions. 1987 Aug;21(3-4):262-5. [Article]
- Uphill PF: A comparison of the effects of tixocortol pivalate (JO 1016), beclomethasone dipropionate and hydrocortisone acetate on the activation of lymphocytes. Arzneimittelforschung. 1981;31(3):459-62. [Article]
- Rietschel R. and Fowler J. (2008). Fisher's contact dermatitis. BC Decker.
- Rainsford K. and Velo G. (1989). New developments in antirheumatic therapy. Kluwer Academic Publishers.
- Chemotechnique diagnostics [Link]
- Clinical experience with tixocortol pivalate [Link]
- External Links
- PubChem Compound
- 162955
- PubChem Substance
- 310265018
- ChemSpider
- 143053
- 57257
- ChEBI
- 63560
- ZINC
- ZINC000005138848
- Wikipedia
- Tixocortol
- MSDS
- Download (26.7 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
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Spray Nasal 1 g/100g Suspension Rectal 250 mg / 100 mL Kit Cutaneous - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 50-55ºC 'MSDS' boiling point (°C) 607ºC at 760 mmHg 'MSDS' water solubility Insoluble 'MSDS' logP 4.48 'MSDS' - Predicted Properties
Property Value Source Water Solubility 0.0428 mg/mL ALOGPS logP 2.42 ALOGPS logP 2.32 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 9.57 Chemaxon pKa (Strongest Basic) -2.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 74.6 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 103.53 m3·mol-1 Chemaxon Polarizability 41.96 Å3 Chemaxon Number of Rings 4 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03fu-0009000000-0c1cec877e3d47171bce Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-002f-0009000000-89d5a489676552917c54 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03fu-0639000000-fa14fd38e3d7c0edce41 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-1009000000-75a044361dd73cfa22dd Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0f79-0059000000-ebc071b851379119019d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05tf-0950000000-2b36a2063b97fdb0346a Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 189.26814 predictedDeepCCS 1.0 (2019) [M+H]+ 191.16356 predictedDeepCCS 1.0 (2019) [M+Na]+ 197.76515 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Zinc ion binding
- Specific Function
- Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
- Gene Name
- NR3C1
- Uniprot ID
- P04150
- Uniprot Name
- Glucocorticoid receptor
- Molecular Weight
- 85658.57 Da
References
- Barnes PJ: How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006 Jun;148(3):245-54. doi: 10.1038/sj.bjp.0706736. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Stimulator
- General Function
- Transcription factor binding
- Specific Function
- Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
- Gene Name
- HDAC2
- Uniprot ID
- Q92769
- Uniprot Name
- Histone deacetylase 2
- Molecular Weight
- 55363.855 Da
References
- Barnes PJ: How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006 Jun;148(3):245-54. doi: 10.1038/sj.bjp.0706736. [Article]
Drug created at September 15, 2015 21:31 / Updated at December 02, 2023 07:01