Effects of the CYP2C91/13 Genotype on the Pharmacokinetics of Lornoxicam

被引：26

作者：

Choi, Chang-Ik ^{[1
]}

Kim, Mi-Jeong ^{[1
]}

Jang, Choon-Gon ^{[1
]}

Park, Young-Seo ^{[2
]}

Bae, Jung-Woo ^{[1
,3
]}

Lee, Seok-Yong ^{[1
]}

机构：

[1] Sungkyunkwan Univ, Sch Pharm, Suwon 440746, South Korea

[2] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[3] Keimyung Univ, Coll Pharm, Taegu, South Korea

来源：

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY | 2011年 / 109卷 / 06期

关键词：

CYTOCHROME P4502C9; CYP2C9; ALLELE; POLYMORPHISMS; FREQUENCIES; JAPANESE;

D O I：

10.1111/j.1742-7843.2011.00751.x

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Lornoxicam is extensively metabolized by CYP2C9, and a CYP2C9*13 is one of the principal variant alleles in East Asian populations. The aim of this study was to evaluate the effects of CYP2C9*1/*13 on the pharmacokinetic parameters of lornoxicam in healthy individuals. A single oral dose of 8 mg lornoxicam was given to 22 Korean volunteers with different CYP2C9 genotypes (8, 8 and 6 carriers of CYP2C9*1/*1, *1/*3 and *1/*13 genotypes, respectively). Lornoxicam and 5'-hydroxylornoxicam levels were analysed using HPLC-UV in plasma samples collected up to 24 hr after taking the drug. In individuals with CYP2C9*1/*13, lornoxicam had a higher Cmax (p < 0.001), a longer half-life (p < 0.001), a lower oral clearance (p < 0.001) and a higher area under the plasma concentration-time curve from zero to infinity (AUCinf) than in CYP2C9*1/*1 individuals (p < 0.001). The Cmax and AUCinf of 5'-hydroxylornoxicam were lower in CYP2C9*1/*13 individuals than in CYP2C9*1/*1 individuals, but the half-life of 5'-hydroxylornoxicam did not differ between the two groups. The half-life, oral clearance and AUCinf of lornoxicam were similar in individuals with CYP2C9*1/*13 and those with CYP2C9*1/*3. The Cmax, half-life and AUCinf of 5'-hydroxylornoxicam were also similar in both groups, although Cmax was higher in CYP2C9*1/*13 individuals (p < 0.01). A CYP2C9*1/*13 genotype markedly reduced the conversion of lornoxicam to 5'-hydroxylornoxicam, to a similar extent as that observed with the CYP2C9*1/*3 genotype.

引用

页码：476 / 480

页数：5

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Effects of the CYP2C9*1/*13 Genotype on the Pharmacokinetics of Lornoxicam

Effects of the CYP2C91/13 Genotype on the Pharmacokinetics of Lornoxicam