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The CYP2A6*4 Allele Is Determinant of S‐1 Pharmacokinetics in Japanese Patients With Non‐small‐cell Lung Cancer
Author(s) -
Kaida Y,
Inui N,
Suda T,
Nakamura H,
Watanabe H,
Chida K
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100484
Subject(s) - tegafur , cyp2a6 , pharmacokinetics , allele , genotyping , lung cancer , prodrug , pharmacology , medicine , polymorphism (computer science) , cancer , gastroenterology , genotype , biology , genetics , metabolism , gene , cytochrome p450 , cyp1a2
S‐1 is an oral fluorouracil anticancer drug that contains the 5‐FU prodrug tegafur. Tegafur has been shown to be converted enzymatically to 5‐FU to exert its antitumor effect, and this conversion is principally catalyzed by CYP2A6. Forty‐six non‐small‐cell lung cancer patients were enrolled. The frequencies of the CYP2A6*4C, CYP2A6*7, and CYP2A6*9 alleles were 17.4, 19.6, and 15.2%, respectively. In the S‐1 pharmacokinetic analysis, the area under the concentration–time curve from 0 to 10 h (AUC 0–10 ) ratios of 5‐FU/tegafur showed large interindividual variabilities, ranging from 5.14 to 112.6. The AUC 0–10 for tegafur was 1.5‐fold higher in patients with the CYP2A6*4C allele than in patients without the CYP2A6*4C allele P < 0.05). Furthermore, patients with the CYP2A6*4C allele had a significantly lower maximum plasma concentration (102.6 ± 32.9 ng/ml) for 5‐FU than patients without the CYP2A6*4C allele (157.0 ± 65.5 ng/ml, P < 0.05). Genotyping of CYP2A6 polymorphisms may provide vital information for effective cancer therapy using S‐1. Clinical Pharmacology & Therapeutics (2008); 83 , 4, 589–594. doi: 10.1038/sj.clpt.6100484