B01AE03 - Argatroban |
Propably not porphyrinogenic |
PNP |
Rationale
Not found to affect the activity of CYP- enzymes. Beside some adverse effect that might restrict food intake, like nausea, no potentially porphyrinogenic effects are suspected for argatroban.
Chemical description
Synthetic L-arginine derivative with quinolinyl-sulfonyl piperideine-carbolic acid functions. The sulfonamide functional group is not coupled to a benzamine function, and therefore argatroban does not contain the chemical sub-structure associated with other porphyrinogenic sulfonamides.
Therapeutic characteristics
Argatroban is used for anticoagulation in patients with heparin-induced platelet deficiency, and in need of antithrombotic therapy. It is administered as an intravenous infusion. Adverse effects of possible relevance to porphyria are nausea and vomiting.
Hepatic exposure
Probably not significant.
Metabolism and pharmakokinetics
Mainly distributed to the extracellular compartment. The binding to albumin and acid glycoprotein is 20 and 34 per cent, respectively. Elimination half time is about 50 minutes. Steady state is reached after 1-3 hours of infusion. The metabolism is not fully elucidated. Three metabolites are identified generated via hydroxylation and aromatization of the methyl-quinoline ring. In vitro, Cyp3A4 and 3A5 show to generate these metabolites, but CYP-enzymes is not thought to be a significant contributor to the elimination of argatroban in vivo.
References
- Scientific articles
- Cruz-González I, López-Jiménez R et al, Pharmacokinetic evaluation of argatroban for the treatment of acute coronary syndrome. Expert Opin Drug Metab Toxicol. 2012 Nov; 8(11):1483-93. #1172
- Kleinschmidt S, Stephan B, et al, Argatroban: pharmacological properties and anaesthesiological aspects. Anaesthesist. 2006 Apr; 55(4):443-50. #1173
- McKeage K, Plosker GL, Argatroban. Drugs 2001; 61(4):515-522. PMID 11324681. #4370
- Tran JQ, Di Cicco RA et al, Assessment of the potential pharmacokinetic and pharmacodynamic interactions between erythromycin and argatroban. J Clin Pharmacol. 1999 May; 39(5):513-9. #1177
- Drug interaction databases
- Lexicomp Online. Martindale: The Complete Drug Reference. Argatroban. Accessed: 04.12.12. #1174
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Exembol. #1176
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