期刊
CLINICAL THERAPEUTICS
卷 25, 期 5, 页码 1407-1419出版社
ELSEVIER
DOI: 10.1016/S0149-2918(03)80128-5
关键词
emesis; chemotherapy; 5-HT3-receptor antagonist; CINV
Background: The neurokinin-1-receptor antagonist aprepitant, when given in combination with a corticosteroid and a 5-hydroxytryptamine type 3 (5-HT3)-receptor antagonist, has been shown to be effective for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Objective: Two studies were conducted to determine whether concomitant administration of aprepitant altered the pharmacokinetic profiles of ondansetron and granisetron, two 5-HT3-receptor antagonists commonly used as antiemetic therapy for CINV Methods: The 2 studies were randomized, open-label, crossover trials conducted in healthy subjects aged between 18 and 46 years. Study I involved the following 2 treatment regimens: aprepitant 375 mg PO, dexamethasone 20 mg PO, and ondansetron 32 mg IV on day 1, followed by aprepitant 250 mg PO and dexamethasone 8 mg PO on days 2 through 5; and dexamethasone 20 mg PO and ondansetron 32 mg IV on day 1, followed by dexamethasone 8 mg PO on days 2 through 5. Study 2 involved the following 2 treatment regimens: aprepitant 125 mg PO with granisetron 2 mg PO on day 1, followed by aprepitant 80 mg PO on days 2 and 3; and granisetron 2 mg PO on day 1 only Individual plasma samples were used to estimate area under the plasma concentration-time curve from time zero to infinity (AUC(0-infinity)), peak plasma concentration, and apparent terminal elimination half-life (t(1/2)) of both ondansetron and granisetron. Results: Study 1 included 19 subjects (10 women, 9 men), and study 2 included 18 subjects (11 men, 7 women). Coadministration of aprepitant 375 mg produced a small but statistically significant increase in the AUC(0-infinity) for intravenous ondansetron (from 1268.3 to 1456.5 ng.h/mL; P = 0.019), with no significant effect on peak concentration at the end of the infusion (360.8 ng/mL with aprepitant vs 408.4 ng/mL without) or t(1/2) (5.0 vs 4.5 hours, respectively). Coadministration of aprepitant 125 mg/80 mg did not alter the mean pharmacokinetic characteristics of oral granisetron (AUC(0-infinity), 101.4 ng.h/mL with aprepitant vs 92.2 ng.h/mL without; maximum plasma concentration, 9.0 ng/mL with and without aprepitant; time to maximum plasma concentration, both 3.0 hours; t(1/2), 6.5 vs 6.9 hours, respectively). Conclusion: Concomitant administration of aprepitant had no clinically significant effect on the mean pharmacokinetic characteristics of either ondansetron or granisetron in these healthy subjects. Copyright (C) 2003 Excerpta Medica, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据