N07BA03 - Varenicline |
Propably not porphyrinogenic |
PNP |
Rationale
Probably insignificant hepatocyte load. Only limited metabolism, no induction or inhibition of CYP 3A4 or 2C9. No clinical reports available on use in acute porphyria.
Chemical description
7,8,9,10-tetrahydro-6,10-methano-6 H -pyrazino[2,3-h][3]benzazepine. Highly soluble in water.
Therapeutic characteristics
Partial agonist selective for alpha 4 beta 2 nicotinic acetylcholine receptor subtypes. Varenicline binds with high affinity and selectivity at alpha 4 beta 2 neuronal nicotinic acetylcholine receptors. Common adverse reactions that can be confused with acute porphyria are insomnia, gastrointestinal disturbances (for example nausea, obstipation, diarrhoea etc), tiredness.
Hepatic exposure
Probably insignificant hepatic exposure (Obach RS 2006).
Metabolism and pharmakokinetics
Less than 10 % is metabolized, by glucuronidation and oxidation. Details on pathway for metabolism is not known. Elimination half life is approximately 24 hours. CYP 2C9 and 3A4 is not inhibited by varenicline. CYP 3A4 is not induced by varenicline. CYP 2C9 is probably not induced as the pharmacokinetics of the substrate warfarin is not affected by concomitant varenicline treatment (Burstein AH 2007).
Published experience
No reports of clinical experience are located.
References
- Scientific articles
- Burstein AH, Clark DJ et al. Lack of pharmacokinetic and pharmacodynamic interactions between a smoking cessation therapy, varenicline, and warfarin: an in vivo and in vitro study. J Clin Pharmacol 2007;47(11):1421-9. #3376
- Obach RS, Reed-Hagen AE et al. Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos 2006;34(1):121-30. PMID 16221753. #3375
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