Pharmacokinetics and Bioequivalence Evaluation of Two Voriconazole tablets: an Open-Label, Single-Dose, Randomized, Two-Way Crossover Study in Healthy Chinese Male Volunteers
Xuewen Qiu, Rongfeng Xiang, Qing Dai, Bo Yang, Lirong Xiong, Yangjing Ou, Min Tang, Yongchuan Chen*
Department of Pharmacy, Southwest hospital, Chongqing, China, 40003
- *Corresponding Author:
- Yongchuan Chen
Department of Pharmacy, Southwest hospital
29TH, Gaotangyan Street, Shapingba District
Chongqing, China, 40003
E-mail: [email protected]
Received Date: April 19, 2012; Accepted Date: May 19, 2012; Published Date: May 21, 2012
Citation: Qiu X, Xiang R, Dai Q, Yang B, Xiong L, et al. (2012) Pharmacokinetics and Bioequivalence Evaluation of Two Voriconazole tablets: an Open-Label, Single-Dose, Randomized, Two-Way Crossover Study in Healthy Chinese Male Volunteers. J Bioequiv Availab 4: 044-047. doi: 10.4172/jbb.10000110
Copyright: © 2012 Qiu X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The aim of this study was to assess and compare the pharmacokinetic properties, bioavailability, and bioequivalence of a newly developed tablet of voriconazole with those of an established branded formulation in healthy Chinese adult male volunteers. An open-label, single-dose, randomized, 2-way crossover study was conducted in fasted healthy Chinese male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive one tablet (200 mg) of the test or reference formulations, followed by a 1-week washout period and administration of the alternate formulations. Plasma samples were collected over 36 hours and analyzed by HPLC. The Voriconazole plasma concentrationÃ¯Â¿Â½time curves were used to obtain pharmacokinetic parameters including AUC0Ã¯Â¿Â½t, AUC0Ã¯Â¿Â½∞, Cmax and Tmax. The criteria for bioequivalence were 90% CIs of 80% to 125% for AUC and 70% to 143% for Cmax, and no significant differences for Tmax with a non-parameter test, according to guidelines of the SFDA of China. Tolerability was based on the recording of adverse events (AEs). A total of 19 volunteers were included in the study. The mean (SD) Cmax, Tmax, AUC0Ã¯Â¿Â½t, and AUC0Ã¯Â¿Â½∞ values after administration of the test and reference formulation, respectively, were as follows: 925.73(356.11) versus 1040.25(448.93) ng/mL, 1.57(0.98) versus 1.38(0.96) hours, 5304.97(3072.25) versus 5141.63(2976.92) ng/mL/h, and 5783.21(3266.86) versus 5520.69(3148.42) ng/mL/h. The relative bioavailability of the test formulation was 103.2% by mean AUC0Ã¯Â¿Â½t and 104.8% by mean AUC0−∞. The 90% CIs for the ratios of Cmax, AUC0Ã¯Â¿Â½t, and AUC0−∞ were 77.3% to 122.7%, 85.7% to 114.3%, and 83.6% to 116.4%, respectively, meeting the predetermined criteria for bioequivalence. No drug-related AEs were observed. In this study the test and reference formulations had similar PK parameters and similar plasma concentration-time profiles and the test formulations met the regulatory criteria for bioequivalence to the established reference formulations based on the rate and extent of absorption. Both formulations were well tolerated.