Lack of bioequivalence between two aciclovir tablets in healthy subjects.
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 microg/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 (AUC(12)) and from time 0 to infinity (AUC(infinity)), and plasma half-life following administration of the test product were 999.6 microg/L, 2.08 h, 4911.2 microg/L . h, 5417.7 microg/L . h and 3.08 h, respectively, and for the reference product 775.8 microg/L, 2.58 h, 3862.1 microg/L . h, 4295.4 microg/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 AUC(12) (90% CI) and AUC(infinity) (90% CI) were 1.26 (99.7, 159.1) and 1.24 (98.9, 155.6), respectively. Therefore, the 90% CIs of C(max), AUC(12) and AUC(infinity) were not within the acceptable range of 80 and 125 suggested by the US FDA bioequivalence guideline.


CONCLUSIONS
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.
Amini
Hossein
H
Department of Physiology and Pharmacology, Cardiovascular Research Center, Golestan University of Medical Sciences, Gorgan, Iran. hamini@sbmu.ac.ir
Javan
Mohammad
M
Gazerani
Parisa
P
Ghaffari
Alireza
A
Ahmadiani
Abolhassan
A
D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008657:Metabolic Clearance Rate; D013607:Tablets; D013810:Therapeutic Equivalency
D000998:Antiviral Agents; D013607:Tablets; D000212:Acyclovir