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Effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects.

Abstract：

OBJECTIVE:To evaluate the effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects. METHODS:A single 5-mg capsule of tropisetron was administered orally to 13 healthy subjects. Plasma concentrations were determined by validated HPLC procedures and data were analyzed by using noncompartmental linear PK methods. Four alleles, CYP2D6*1, CYP2D6*2 x2, CYP2D6*5, and CYP2D6*10, were identified by PCR. RESULTS:Thirteen subjects, consisting of two homozygous carriers of the wild type allele ( *1/*1), four heterozygous carriers of poor metabolizer (PM)-associated allele (* 1/*10), six homozygous carriers of PM-associated alleles (four with *10/*10 and two with *5/*10), and one carrier of a duplicated allele *1/*2 x2. All tested pharmacokinetic parameters (AUC(inf), AUC(inf)(NL70), Cmax, Cmax(NL70), T(1/2), and Tec) were significantly different among four different genotypic groups. The mean AUCs of carriers with the heterozygous PM-associated allele and the homozygous PM-associated allele were 1.9- and 6.8-higher than those of carriers with the wild type allele, respectively. In contrast, the mean AUC of carriers with a duplicated allele was 0.5-fold lower than that of those carriers with the wild type allele. CONCLUSION:The presence of CYP2D6*5, CYP2D6*10, and CYP2D6*2 x2 has an important impact on the pharmacokinetics of tropisetron, which may influence clinical response to tropisetron therapy.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Kim MK,Cho JY,Lim HS,Hong KS,Chung JY,Bae KS,Oh DS,Shin SG,Lee SH,Lee DH,Min B,Jang IJ

doi

10.1007/s00228-003-0595-1

subject

Has Abstract

pub_date

2003-06-01 00:00:00

pages

111-6

issue

2

eissn

0031-6970

issn

1432-1041

journal_volume

59

pub_type

杂志文章

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