Stereoselective pharmacokinetics of oxybutynin and N-desethyloxybutynin in vitro and in vivo.

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Mizushima H, Takanaka K, Abe K, Fukazawa I, Ishizuka H

Stereoselective pharmacokinetics of oxybutynin and N-desethyloxybutynin in vitro and in vivo.

Xenobiotica. 2007 Jan;37(1):59-73. doi: 10.1080/00498250600976088.

PubMed ID

17178634 [ View in PubMed

]

Abstract

In vitro studies and the multiple applications of an oxybutynin (OXY) transdermal delivery system to Japanese healthy volunteers were conducted to characterize the stereoselectivity in the pharmacokinetics of OXY and its metabolite, N-desethyloxybutynin (DEOB). In human liver microsomes, (R)-OXY and (R)-DEOB were eliminated slightly slower than the corresponding (S)-enantiomers. The production of DEOB from OXY for the (R)-enantiomer was also slower than that for the (S)-enantiomer. In human P450-expressing liver microsomes, OXY was metabolized mainly by CYP3A4 among five cytochrome P450s (CYPs) tested (CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5) and the kinetics were slightly different for the enantiomer. The unbound fraction of (R)-OXY in plasma was almost two times higher than that of (S)-OXY, whereas (R)-DEOB was bound to plasma protein more than (S)-DEOB. No differences were observed in the blood-plasma concentration ratios for the enantiomers. After multiple applications of the transdermal delivery system, the plasma concentrations of (R)-OXY were lower than those of (S)-OXY. These data indicate that for the stereoselectivity of OXY, the unbound fraction of each OXY enantiomer was a major factor and the metabolism in liver had a minimal effect.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Oxybutynin	Cytochrome P450 3A5	Protein	Humans	Unknown	Substrate	Details