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

Article Details

Citation

Copy to clipboard

Yaich M, Popon M, Medard Y, Aigrain EJ

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

Pharmacogenetics. 1998 Oct;8(5):449-51.

PubMed ID

9825837 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Oxybutynin	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details