Drug Design, Development and Therapy (Mar 2020)
Comparison of Pharmacokinetics of Aprepitant in Healthy Chinese and Caucasian Subjects
Abstract
Meng-Jie Yang, Hong-Rong Xu, Hui Li, Wei-Li Chen, Fei Yuan, Xue-Ning Li Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Xue-Ning LiDepartment of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of ChinaTel +86 21 31587861Fax +86 21 64437963Email [email protected]: Aprepitant is used to prevent nausea and vomiting associated with moderately and highly emetogenic chemotherapy. In this open-label, 2-period study, the safety, tolerability, and pharmacokinetics (PK) of aprepitant (EMEND®) were evaluated in healthy Chinese and Caucasian subjects.Patients and Methods: Twelve Chinese and 12 Caucasian subjects were to receive a 125 mg single-dose of aprepitant during period 1; subsequently, after 15 days washout, only Chinese subjects were to receive the 3-day regimen in period 2. In each period, serial blood samples were collected and analyzed by a validated liquid chromatographic and mass spectrometric method to characterize aprepitant PK across both groups.Results: In both Chinese and Caucasian subjects, there were no serious adverse events. AUC0-∞, Cmax, Tmax, and t1/2 were largely comparable between the two ethnicities. Comparing the result of period 1 in Chinese and Caucasian subjects, the geometric least-squares mean maximum plasma concentrations (Cmax) were 1482 ng/mL and 1435 ng/mL, and the area under the concentration–time curve (AUC0-∞) 34,035 hr·ng/mL and 34,188 hr·ng/mL. In period 2, the geometric mean AUC0– 24 on Day 1 and Day 3 were 19,446 hr·ng/mL and 27,843 hr·ng/mL, and the geometric mean Cmax on Day 1 and Day 3 were 1423 ng/mL and 1757 ng/mL, respectively.Conclusion: Aprepitant is generally safe and well tolerated in healthy Chinese and Caucasian subjects. Aprepitant PK is comparable between Chinese and Caucasian subjects following single-dose administration. The PK following a clinical 3-day regimen on healthy Chinese subjects has been characterized.Keywords: pharmacokinetics, aprepitant, chemotherapy-induced nausea and vomiting, ethnicity, healthy subjects
