PMID: 9825837Nov 24, 1998Paper

In-vitro cytochrome P450 dependent metabolism of oxybutynin to N-deethyloxybutynin in humans

Pharmacogenetics
M YaïchE J Aigrain

Abstract

Oxybutynin (Ditropan), a direct antagonist of acetylcholine on muscarinic receptors, is administered in children for the treatment of vesical immaturity and is responsible for atropinic adverse effects, which are more frequent in paediatric than in adult patients. Oxybutynin is metabolized by oxidation to N-desethyloxybutynin, a stable and toxic metabolite, and previous results in vivo have suggested that cytochrome P450 2D6 (CYP2D6) may be involved in this pathway of metabolism. We used human liver microsomes genotyped as extensive metabolizers for CYP2D6 to determine the kinetic parameters of N-desethyloxybutynin formation: Km was 16.5+/-5.2 microM and Vmax was 76.8+/-3.7 mmol/mg/h. Quinidine and anti-liver kidney microsome antibody type I had no inhibitory effects on N-desethyloxybutynin formation, demonstrating that CYP2D6 has no role in oxybutynin metabolism. The effects of specific inhibitors of other cytochromes P450 were also investigated. Recombinant human CYP 3A4 but not 2B6, 2D6, 2C8 and 2E1, displayed significant N-desethylation activity. Our results demonstrate that the CYP3A subfamily, and not CYP2D6, is involved in N-desethyloxybutynin formation.

Citations

Oct 6, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Martin C Michel, Sharath S Hegde
Oct 25, 2008·Current Urology Reports·Karl-Erik AnderssonRoberto Soler
Aug 23, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·A D WoolfsonR J Gallagher
Nov 11, 2003·Clinical Pharmacokinetics·David R P Guay
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Dec 3, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Andrés Olivares-MoralesAmin Rostami-Hodjegan
Apr 22, 2015·Pharmacogenomics·Henrik Berg RasmussenUNKNOWN INDICES Consortium
Sep 17, 2013·International Journal of Pharmaceutics·Fatmanur Tuğcu-DemirözDeniz Erdoğan
Nov 9, 2005·Bioorganic & Medicinal Chemistry Letters·Jean-Philippe StarckMichel Guyaux
Jun 14, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Silvio AprileGiorgio Grosa
Aug 28, 2018·Current Drug Discovery Technologies·Maria A Grishina, Vladimir A Potemkin
Apr 11, 2001·Therapeutic Drug Monitoring·J E Springate
Dec 21, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H MizushimaH Ishizuka
May 29, 2009·Journal of Chemical Information and Modeling·Vladimir A PotemkinMaria A Grishina
Aug 22, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Zong-Ling XiaTong-Wei Yao

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