生物等效性和生物利用度杂志

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Comparative Pharmacokinetics, Safety and Tolerability Evaluation of Acyclovir IR 800 Mg Tablet in Healthy Indian Adult Volunteers Under Fasting and Non-fasting Conditions

P Susantakumar, Ajay Gaur and Piush Sharma

Objectives: This study was designed to determine the comparative pharmacokinetics, safety and tolerability of test acyclovir 800mg IR formulation with reference product (Zovirax® 800mg IR Tablet) after single dose administration under fasting and non-fasting conditions in 36 male and female adult subjects. Methods: Open label, balanced, randomized, two-sequence, single-dose, two-way crossover study design in healthy Indian adult volunteers with a washout period of at least 7 days was used. Each subject received an acyclovir test or reference product respectively. Blood samples were collected before dosing and at various time points up to 24 hours after dosing. Plasma samples were analyzed by validated liquid chromatography with tandem mass spectrometry method. The pharmacokinetic parameters C max , T max , MRT, AUC 0-t , and AUC 0-∞ were analyzed using non-compartment model. Drug safety and tolerability were assessed. Results: Total 36 and 34 subjects in fasting in non-fasting study had completed both treatment periods. Two subjects were dropout due to family reason. No statistical significance difference of pharmacokinetic parameters C max , AUC 0-t and AUC 0-∞ between test and reference product. Food dose not affects the rate and extent of acyclovir absorption in systemic circulation was observed in both fasting and non-fasting study. The significant sequence (carry-over) effects of AUC 0-t and AUC 0-∞ were acceptable due to non detectable drug in pre-dose samples in analyzed subjects. Total 07 subjects reported 26 adverse events during the fasting study, and 06 subjects reported adverse events during the non-fasting study. Acyclovir was found safe and well tolerated by all subjects who had completed the study in good health conditions. Conclusion: The single dose pharmacokinetics, safety and tolerability study found that the test formulation acyclovir 800mg immediate release tablets were comparable to the reference product at rate and extent of absorption under fasting and non-fasting conditions in healthy adult subjects according to the USFDA regulatory guidance.