生物学的同等性とバイオアベイラビリティのジャーナル

概要

An Assessment of the Pharmacokinetics and Tolerability of Single-Ascending Doses of Desvenlafaxine Administered to Healthy Chinese Subjects

Lingling Guan, Huafang Li, Zhangjing Chen, Glen Frick and Alice Nichols

Desvenlafaxine (administered as desvenlafaxine succinate) exhibited linear pharmacokinetics after singledose administration in a US population. The current study assessed the pharmacokinetics and tolerability of singleascending doses of desvenlafaxine in Chinese subjects. Healthy adult subjects of Chinese descent living in China were randomly assigned to receive either a single dose of desvenlafaxine 50, 100, 200 mg, or placebo in this sponsor-unblinded, inpatient, ascending-dose study. Desvenlafaxine concentrations in urine and plasma were measured using a validated liquid chromatography/tandem mass spectrometry method. Peak plasma concentration (Cmax) and time to Cmax (tmax) were determined directly from observed data, and area under the plasma concentrationversus- time curve (AUC) was computed. Dose proportionality for Cmax and AUC was examined using a power model. Tolerability was assessed through adverse event (AE) reporting. Thirty-six subjects were enrolled. The Cmax of desvenlafaxine increased 138% between the 50 mg (109 ng/mL) and 100 mg (259 ng/mL) doses. The Cmax for subjects receiving desvenlafaxine 200 mg was 654 ng/mL, a 153% increase compared with the 100 mg dose. The AUC of desvenlafaxine increased 127% from the 50 mg dose (2,520 ng•hr/mL) to the 100 mg dose (5,720 ng•hr/ mL), and 126% between the 100 mg and 200 mg (12,900 ng•hr/mL) doses. The power model analysis indicated dose proportionality for AUC, but not for Cmax. No serious AEs were reported. Desvenlafaxine was generally well tolerated in healthy Chinese subjects, and its exposure (AUC) was dose-proportional. Results from this study and studies in US, European, and Japanese populations indicate that the pharmacokinetics of desvenlafaxine were comparable between these ethnic groups.