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KMID : 0043320190420020182
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Archives of Pharmacal Research
2019 Volume.42 No. 2 p.182 ~ p.190
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Influence of CYP2D6 genetic polymorphism on pharmacokinetics of active moiety of tolterodine
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Byeon Ji-Yeong
Lee Choong-Min
Lee Yea-Jin
Kim Young-Hoon
Kim Se-Hyung
Jung Eui-Hyun
Chae Won-Ki
Lee Yun-Jeong
Jang Choon-Gon
Lee Seok-Yong
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Abstract
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Tolterodine is metabolized to an active 5-hydroxymethyl tolterodine (5-HMT) by CYP2D6. This study investigated the relationship between CYP2D6 genotypes and pharmacokinetics of tolterodine and its active metabolite in healthy Korean subjects. All volunteers were genotyped for CYP2D6 and divided into four different genotype groups (CYP2D6*wt/*wt [*wt?=?*1 or *2], CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10). Each subject received a single oral dose of tolterodine tartrate (2 mg) in single-dose phase of the study. After the single-dose phase of the study, the same subjects received a single oral dose of tolterodine tartrate (2 mg) once daily for 1 week during multiple-dose tolterodine administration phase. Plasma concentrations of tolterodine and 5-HMT were measured by using liquid chromatography-tandem mass spectrometry method. Our study demonstrated that plasma exposure of tolterodine in CYP2D6*10/*10 and CYP2D6*5/*10 group significantly increased, compared with CYP2D6*wt/*wt group (P?
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KEYWORD
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Tolterodine, 5-hydroxymethyl tolterodine, CYP2D6, Polymorphisms, Pharmacokinetics
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