Abe Masaichi, Smith James, Urae Akinori, Barrett Joanne, Kinoshita Haruki, Rayner Craig R
Department of Clinical Pharmacology, Chugai Clinical Research Center Co. Ltd, Tokyo, Japan.
Ann Pharmacother. 2006 Oct;40(10):1724-30. doi: 10.1345/aph.1H174. Epub 2006 Aug 29.
Pharmacokinetic studies of oseltamivir in very elderly patients (> or = 80 y) have not previously been performed.
To compare the pharmacokinetics of oseltamivir and the active carboxylate metabolite in healthy young and very elderly Japanese subjects.
Young (20-35 y, fasting, n = 7) and very elderly subjects (> or = 80 y, fed, n = 5) were enrolled in single-center studies and received a single oral dose of oseltamivir 75 mg. Plasma and urine samples were collected (24 h) for pharmacokinetic analysis, and safety was assessed.
The time to maximum plasma concentration (tmax) for oseltamivir was delayed in the very elderly compared with the young subjects (2.30 vs 0.71 h, respectively). Furthermore, oseltamivir maximum plasma concentration (Cmax) and AUC(inf) were 52% and 80% higher, respectively, in the very elderly compared with the young subjects. Oral clearance was 45% lower in elderly patients, possibly due to the effects of administration of oseltamivir with a meal. For the active metabolite, oseltamivir carboxylate, Cmax and AUC(inf) values were, respectively, 22% and 91% higher in the very elderly subjects than in the young subjects, while oral clearance was 50% lower in the elderly population. The increased exposure of the active metabolite is likely to correlate with an age-related decline in renal function. For both oseltamivir and the active metabolite, there was large interpatient variability in the Cmax values. The data reported here indicate that oseltamivir would be effective in both of these populations, as trough concentrations for the active metabolite at 12 and 24 hours exceeded the 50% inhibitory concentration against the neuraminidase of influenza A and B isolates by more than 50-fold. Oseltamivir was well tolerated in both groups.
Exposures (AUC(inf)) to both the parent drug and active metabolite were increased by more than 80% in the small number of very elderly subjects presented here. However, oseltamivir was well tolerated by these subjects.
此前尚未对80岁及以上的高龄患者进行过奥司他韦的药代动力学研究。
比较健康年轻和高龄日本受试者中奥司他韦及其活性羧酸盐代谢物的药代动力学。
年轻受试者（20 - 35岁，空腹，n = 7）和高龄受试者（80岁及以上，非空腹，n = 5）纳入单中心研究，口服单剂量75 mg奥司他韦。采集血浆和尿液样本（24小时）进行药代动力学分析，并评估安全性。
与年轻受试者相比，高龄受试者中奥司他韦的达峰时间（tmax）延迟（分别为2.30小时和0.71小时）。此外，高龄受试者中奥司他韦的最大血浆浓度（Cmax）和药时曲线下面积（AUC(inf)）分别比年轻受试者高52%和80%。老年患者的口服清除率低45%，可能是由于与食物同服奥司他韦的影响。对于活性代谢物奥司他韦羧酸盐，高龄受试者的Cmax和AUC(inf)值分别比年轻受试者高22%和91%，而老年人群的口服清除率低50%。活性代谢物暴露增加可能与年龄相关的肾功能下降有关。对于奥司他韦及其活性代谢物，Cmax值在患者间均存在较大差异。此处报告的数据表明，奥司他韦在这两类人群中均有效，因为活性代谢物在12小时和24小时的谷浓度超过了对甲型和乙型流感病毒分离株神经氨酸酶50%抑制浓度的50倍以上。两组对奥司他韦的耐受性均良好。
在此处少数高龄受试者中，母体药物及其活性代谢物的暴露量（AUC(inf)）均增加了80%以上。然而，这些受试者对奥司他韦耐受性良好。
