Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients
Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients
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DOI：
10.1111/j.1349-7006.2010.01793.x
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发表时间：
2011-02-01
期刊：
影响因子：
5.7
通讯作者：
Rosen, Lee S.
中科院分区：
文献类型：
--
作者：
Chuah, Benjamin;Goh, Boon-Cher;Rosen, Lee S.
S-1是一种口服氟尿嘧啶类抗肿瘤药物，可通过CYP 2A 6转化为5-氟尿嘧啶（5 FU）。我们在两组标准化疗难治性或适用于5 FU的实体肿瘤东亚和高加索患者中前瞻性研究了S-1的药代动力学和药效学，以阐明与CYP 2A 6基因型和表型相关的差异。S-1以30 mg/m（2）b.i.d.口服给药。每21天14天。东亚人中替加氟（P = 0.05）和吉美拉西（P = 0.036）的剂量标准化AUC（0-48）h较高;相反，高加索人中氟-β-丙氨酸的AUC 0 -48 h较高（P = 0.044）。两组的5 FU暴露量相似（P = 0.967）。白人组的平均可替宁：尼古丁比高54%（P = 0.03），与替加氟的口服清除率相关（r = 0.59; P = 0.002）。3 /4级胃肠道毒性在白人中比亚洲人更常见（21% vs 0%）。S-1治疗在高加索人和东亚人之间的5 FU暴露量无显著差异。（Cancer Sci 2011; 102：478-483）
S-1 is an oral fluoropyrimidine anti-neoplastic agent that is converted by CYP2A6 to 5-fluorouracil (5FU). We prospectively studied the pharmacokinetics and pharmacodynamics of S-1 in two groups of East Asian and Caucasian patients with solid malignancy refractory to standard chemotherapy, or for which 5FU was indicated, to elucidate differences in relation to CYP2A6 genotype and phenotype. S-1 was given orally at 30 mg/m(2) b.i.d. for 14 days every 21 days. Dose normalized AUC(0-48) h for tegafur (P = 0.05) and gimeracil (P = 0.036) were higher in East Asians; conversely, AUC0-48 h of fluoro-beta-alanine was higher in Caucasians (P = 0.044). Exposure to 5FU was similar in both groups (P = 0.967). Mean cotinine: nicotine ratio was 54% higher in the Caucasian group (P = 0.03), and correlated with oral clearance of tegafur (r = 0.59; P = 0.002). Grade 3 /4 gastrointestinal toxicities were more common in Caucasians than Asians (21% vs 0%). Treatment with S-1 yields no significant difference in 5FU exposure between Caucasians and East Asians. (Cancer Sci 2011; 102: 478-483)