Schentag Jerome J, Hill George, Chu Tom, Rayner Craig R
University at Buffalo School of Pharmacy, 517 Hochstetter Hall, Buffalo, NY 14260, USA.
J Clin Pharmacol. 2007 Jun;47(6):689-96. doi: 10.1177/0091270007299761. Epub 2007 Apr 24.
The pharmacokinetics of oseltamivir and oseltamivir carboxylate in healthy Japanese (n = 14) and Caucasian (n = 14) males were compared. Subjects in each ethnic group were randomized to twice-daily oral oseltamivir 75 mg, 150 mg, or placebo for 13 doses. Oseltamivir was well tolerated across doses and ethnic groups. Oseltamivir was rapidly absorbed and hydrolyzed to oseltamivir carboxylate in all subjects. The mean plasma concentration-time profiles for oseltamivir and oseltamivir carboxylate were similar in Japanese and Caucasian subjects. At steady state, there was no evidence of any ethnic difference in the individual AUC(0-12) values for oseltamivir or oseltamivir carboxylate. Despite a significant difference in group mean body weight (approximately 20 kg) between the Japanese and Caucasian subjects, there was no evidence that dose-adjusted AUC(0-12) and C(max) for oseltamivir carboxylate were affected by body weight or ethnicity. Day 7 trough concentrations (C(min)) for oseltamivir carboxylate markedly exceeded the IC(50) (50% inhibitory concentration) against influenza A and B isolates. In conclusion, the results of this study support the use of the same dose regimens of oseltamivir in both Caucasian and Japanese subjects because of similarity in pharmacokinetics.
对14名健康日本男性和14名健康高加索男性中奥司他韦及奥司他韦羧酸盐的药代动力学进行了比较。每个种族组的受试者被随机分为每日两次口服75毫克、150毫克奥司他韦或安慰剂，共服用13剂。奥司他韦在不同剂量和种族组中耐受性良好。在所有受试者中，奥司他韦均被迅速吸收并水解为奥司他韦羧酸盐。日本受试者和高加索受试者中奥司他韦及奥司他韦羧酸盐的平均血浆浓度-时间曲线相似。在稳态时，没有证据表明奥司他韦或奥司他韦羧酸盐的个体AUC(0 - 12)值存在种族差异。尽管日本受试者和高加索受试者的组平均体重存在显著差异（约20千克），但没有证据表明奥司他韦羧酸盐的剂量调整后AUC(0 - 12)和C(max)受体重或种族影响。奥司他韦羧酸盐第7天的谷浓度（C(min)）显著超过了对甲型和乙型流感病毒分离株的IC(50)（50%抑制浓度）。总之，由于药代动力学相似，本研究结果支持在高加索和日本受试者中使用相同剂量方案的奥司他韦。
