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

  • Authors:
    • Takashi Hirose
    • Ken-Ichi Fujita
    • Kazuko Nishimura
    • Hiroo Ishida
    • Keishi Yamashita
    • Yu Sunakawa
    • Keiko Mizuno
    • Keisuke Miwa
    • Fumio Nagashima
    • Yusuke Tanigawara
    • Mitsuru Adachi
    • Yasutsuna Sasaki
  • View Affiliations

  • Published online on: August 1, 2010     https://doi.org/10.3892/or_00000889
  • Pages: 529-536
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Abstract

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/m2/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.

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August 2010
Volume 24 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hirose T, Fujita K, Nishimura K, Ishida H, Yamashita K, Sunakawa Y, Mizuno K, Miwa K, Nagashima F, Tanigawara Y, Tanigawara Y, et al: Pharmacokinetics of S-1 and CYP2A6 genotype in Japanese patients with advanced cancer. Oncol Rep 24: 529-536, 2010
APA
Hirose, T., Fujita, K., Nishimura, K., Ishida, H., Yamashita, K., Sunakawa, Y. ... Sasaki, Y. (2010). Pharmacokinetics of S-1 and CYP2A6 genotype in Japanese patients with advanced cancer. Oncology Reports, 24, 529-536. https://doi.org/10.3892/or_00000889
MLA
Hirose, T., Fujita, K., Nishimura, K., Ishida, H., Yamashita, K., Sunakawa, Y., Mizuno, K., Miwa, K., Nagashima, F., Tanigawara, Y., Adachi, M., Sasaki, Y."Pharmacokinetics of S-1 and CYP2A6 genotype in Japanese patients with advanced cancer". Oncology Reports 24.2 (2010): 529-536.
Chicago
Hirose, T., Fujita, K., Nishimura, K., Ishida, H., Yamashita, K., Sunakawa, Y., Mizuno, K., Miwa, K., Nagashima, F., Tanigawara, Y., Adachi, M., Sasaki, Y."Pharmacokinetics of S-1 and CYP2A6 genotype in Japanese patients with advanced cancer". Oncology Reports 24, no. 2 (2010): 529-536. https://doi.org/10.3892/or_00000889