Pharmacokinetic and bioequivalence evaluation of two formulations of levocetirizine 5 mg in healthy thai volunteers

Abstract

Pharmacokinetics of levoceterizine have been studied, however, obtained information was only from the Western people. In addition, the license of this drug formulation was expired few years ago. For approval of this new generic drug, the bioequivalence study is a registration requirement by the Thai Food and Drug Administration. Thus, the objectives of this study were to determine the pharmacokinetics of levocetirizine in healthy Thai volunteers and to compare the pharmacokinetics of a test (new generic; Avocet) and reference (Xyzal®) formulations of levocetirizine 5 mg after single oral administration in healthy Thai volunteers. A single-dose, randomized-sequence, open-label, two-way crossover with a one-week washout period was conducted in 26 fasted volunteers. Levocetirizine was assayed by using a liquid-chromatography tandem mass spectrometry (LC-MS/MS) method. The Cmax, AUC0 t, AUC0-oo, Tmax, and t1/2 evaluated from test drug administration were 226.50 ± 49.70 ng/mL, 1564.96 ± 336.29 ng/L/h, 1821.37 ± 434.38 ng/L/h, 1.00 ± 0.68 h, and 8.36 ± 3.28 h, respectively. The 90% CIs for the test/reference ratios of the log-transformed Cmax, AUC0-t, and AUC0-∞ were 87.39 to 103.05%, 99.27 to 108.63%, and 95.21 to 111.42%, respectively. No serious adverse events were observed during conduct of this study and both formulations were well tolerated. In conclusion, a single 5-mg dose of the test formulation of levocetirizine met the regulatory criteria for bioequivalence to the reference formulation based on the rate and extent of absorption.