Lack of Bioequivalence between Two Aciclovir Tablets in Healthy Subjects

Abstract

Objective:

This study aimed to compare the systemic bioavailability of two aciclovir tablets, Rouz-Aciclovir (test) and Zovirax® (reference), in 12 healthy volunteers.

Methods:

In a crossover design, each subject received a single oral dose of aciclovir 400 mg followed by a 7-day washout period. Plasma concentrations of aciclovir were measured for up to 12 hours using a validated high-performance liquid chromatography method with a lower limit of quantification of 50 μg/L.

Results:

The mean values of maximum plasma concentration (C_max), time to C_max (t_max), area under the plasma concentration-time curve from time 0 to 12 hours (AUC₁₂) and from time 0 to infinity (AUC_∞), and plasma half-life following administration of the test product were 999.6 μg/L, 2.08 h, 4911.2 μg/L · h, 5417.7 μg/L · h and 3.08 h, respectively, and for the reference product 775.8 μg/ L, 2.58 h, 3862.1 μg/L · h, 4295.4 μg/L · h and 3.14 h, respectively. The test/ reference geometric ratio for C_max (90% CI) was 1.30 (97.1, 174.8). The test/ reference geometric ratios for AUC₁₂ (90% CI) and AUC_∞ (90% CI) were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90% CIs of C_max, AUC₁₂ and AUC_∞ were not within the acceptable range of 80 and 125 suggested by the US FDA bioequivalence guideline.

Conclusion:

The results of the present study suggest that the aciclovir test product was not bioequivalent to the reference product. The exact reasons for this remain to be determined. However, we think the difference should be attributed to the difference in the type and amounts of ingredients used in the formulation that probably affect the contact time of aciclovir with the sites of absorption in the gut.