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Pharmacokinetics of S-1 and CYP2A6 genotype in Japanese patients with advanced cancer

jgsun 添加于 2011-4-19 17:34 | 1898 次阅读 | 0 个评论

作者
Hirose T, Fujita K-I, Nishimura K, Ishida H, Yamashita K, Sunakawa Y, Mizuno K, Miwa K, Nagashima F, Tanigawara Y, Adachi M, Sasaki Y
摘要
We developed a population pharmacokinetic (PPK) model of S-1 including the cytochrome P450 (CYP) 2A6 genotype and then used this PPK model to assess the influence of the CYP2A6 genotype on PK parameters of S-1 and the relationship between toxicity and the individual maximum concentrations (Cmax) or the area under the concentration-time curve (AUC) of 5-fluorouracil (5-FU) in Japanese patients with advanced cancer. Fifty-eight patients with advanced cancer were assessed. A dose of 80 mg/m(2)/day of S-1 was given orally. On the basis of the CYP2A6 genotypes (*1, *4, *7 and *9), all patients were classified as having the wild-type, 1 variant allele or 2 variant alleles. The PPK model was established with plasma concentration data for tegafur (FT), 5-chloro-2,4-performed dihydroxypyridine (CDHP) and 5-FU. In patients with 2 variant alleles of CYP2A6, the clearance of FT was 58% less than in patients with the wild-type or 1 variant allele. The AUC of 5-FU correlated with the AUC of CDHP, but not with the AUC of FT. Therefore, the CYP2A6 genotype did not affect the AUC of 5-FU. The individual AUC or Cmax of 5-FU did not differ significantly between patients with grade 3 or 4 toxicities and patients with grade 0-2 toxicities. In conclusion, the CYP2A6 genotype did not affect the AUC of 5-FU, although the clearance of FT was lower in patients with 2 variant alleles of CYP2A6 than in patients with the wild-type or 1 variant allele.
详细资料
- 文献种类:期刊
- 期刊名称: Oncology Reports
- 期刊缩写: Oncol Rep
- 期卷页: 2010年第24卷第2期 529-536页
- 地址: Division of Respiratory Medicine and Allergology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa, Tokyo 142-8666, Japan. thirose@med.showa-u.ac.jp
- ISBN: 1021-335X
- 备注:PMID:20596643
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附件
Pharmacokinetics of S-1 and CYP2A6 genotype in Japanese patients with advanced c
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