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

Bioavailability of Two Different Coated-Tablet Formulations of Valacyclovir of Two Different Strengths (500 mg and 1000 mg) in Healthy Mexican Adult Volunteers

Eduardo Hernandez, Iván Alvarado, Sara Castillo, Ericka López-Bojórquez, Sofía del Castillo-García, Clara Espinosa-Martínez, Victoria Burke-Fraga and Mario González-de la Parra

Valacyclovir is a prodrug of acyclovir. In Mexico, it is indicated for the treatment of herpes zoster and herpes simplex infections. The aims of these 2 studies were to compare the bioavailability and to determine the bioequivalence of 2- test formulations containing 500 mg and 1000 mg of oral valacyclovir. Two separate, single-dose, open-label, randomized, 2-period, crossover studies were conducted. For each study a different set of 26 subjects of both genders was enrolled, with a 7-day washout period. In both studies, the study formulations were administered after a 10-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at baseline, 0.25, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 3, 4, 6, 8, 12 and 24 hours after administration. Plasma concentrations of acyclovir were determined using HPLC coupled to a fluorescence detector. The test and reference formulations were to be considered bioequivalent if the 90% CI for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%. In the study with valacyclovir 500 mg, the 90% CI were 95.24% - 115.33% for C_max, 96.20% - 103.55% for AUC_0-t, 97.12% - 104.34% for AUC_0-∞. In the study with valacyclovir 1000 mg the 90% CI were 86.22%- 100.87% for C_max, 89.11% - 98.50% for AUC_0-t, 89.00% - 98.34% for AUC_0-∞. In both studies, a single dose of the test formulation met the regulatory requirements to assume bioequivalence, based on the rate and extent of absorption.