Purpose: 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. AUC_0-∞, C_max, T_max, and t_1/2 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 (C_max) were 1482 ng/mL and 1435 ng/mL, and the area under the concentration–time curve (AUC_0-∞) 34,035 hr·ng/mL and 34,188 hr·ng/mL. In period 2, the geometric mean AUC_{0– 24} on Day 1 and Day 3 were 19,446 hr·ng/mL and 27,843 hr·ng/mL, and the geometric mean C_max 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