Abstract

Objective: Abacavir sulfate is a synthetic carbocyclic nucleoside analogue indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. The objective of the current study was to determine the bioequivalence between a generic formulation of abacavir and the innovator product. Material and methods: A total of 80 subjects were randomly assigned to receive a single 300 mg oral dose of abacavir sulfate as the generic (Ranbaxy-Abacavir, Ranbaxy Laboratories Ltd., equivalent to 300 mg of abacavir) and innovator (Ziagen, GlaxoSmithKline) tablet formulations in 2-way crossover studies performed under fasting (n = 40) and fed (n = 40) conditions. Multiple blood samples were collected over 14 hours and plasma concentrations of abacavir were assayed using an LC/MS/MS method with a limit of quantitation of 25.0 ng/ml. Pharmacokinetic (PK) parameters were calculated using noncompartmental methods. Results: Under fasting conditions, geometric mean area under the curve from time 0 to the last measurable concentration (AUC0-t), area under the curve extrapolated to infinity (AUC0-¥) and maximum plasma concentrations (Cmax) of abacavir for the generic (5,565 ng × h/ml, 5,668 ng × h/ml and 2,526 ng/ml, respectively) and innovator (5,675 ng × h/ml, 5,770 ng × h/ml and 2,528 ng/ml, respectively) products were very similar. Under fed conditions, mean values of AUC0-t, AUC0-¥ and Cmax for the generic (4,487 ng × h/ml, 4,571 ng × h/ml and 1,841 ng/ml, respectively) and innovator (4,574 ng × h/ml, 4,654 ng × h/ml and 1,781 ng/ml, respectively) formulations were also very similar. Ratios of LSM and 90% confidence intervals of PK parameters between the 2 formulations were within 80.0 – 125.0% under fasting and fed conditions, suggesting that the 2 tablet formulations resulted in similar rate and extent of bioavailability. Adverse events for the generic and innovator products were similar in nature and frequency in the fasting and fed studies. Conclusions: Based on the above results, the generic tablet formulation of abacavir developed by Ranbaxy should be equally effective as the innovator product.

Author Details

Authors

• J.F. Marier¹
• M. Borges¹
• G. Plante¹
• M. DiMarco¹
• G. Morelli¹
• S.K. Tippabhotla²
• T. Vijan²
• A.K. Singla²
• M. Garg²
• T. Monif²

Departments

• ¹ MDS Pharma Services, St.-Laurent, Montreal, Quebec, Canada,
• ² Ranbaxy Laboratories Ltd., Gurgaon, Haryana, India

Address

T. Monif, PhD
Director, Department of Clinical Pharmacology and Pharmacokinetics
Ranbaxy Laboratories Ltd.
Plot No. 20, Sector-18
Udyog Vihar Industrial Area
Gurgaon – 122 001, Haryana, India
Email: [email protected]

Citation