Bioequivalence study of Ribavirin 400 mg tablets in healthy Thai male volunteers under fed conditions J.Vattanarongkup 1 , E. Yoosakul 1 , C. Manamuti 1 , P. Teerawonganan 1 , C. Seeduang 1 , P. Ratnatilaka Na Bhuket 1 , A. Rojanawiwat 2 , B. Karachot 1 , B. Chuasuwan 1 , I. Techatanawat 1* 1 Research and Development Institute, The Government Pharmaceutical Organization, Bangkok, Thailand 2 Clinical Research Center, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand Abstract Ribavirin is a nucleoside analogue that exerts an antiviral activity. It mostly uses as a combination with interferon alfa-2b for hepatitis C treatment. Development of a generic product of ribavirin would be beneft for hepatitis C patient in Thailand. The purpose of this study is to investigate the bioequivalence of the generic formulation, Ribavirin GPO 400 mg tablets compared to an originator, Copegus ® 400 mg tablets. A randomized, single dose, two-way crossover, open-label bioequivalence study in healthy Thai male volunteers under fed conditions with 6 weeks washout period was conducted. The plasma samples were collected and the ribavirin concentration was analyzed using validated liquid chromatography tandem mass spectrometry method. The pharmacokinetic parameters including of area under the plasma concentration time curve from time 0 hour to 72 hours (AUC 0-72 ), the peak plasma concentration (C max ) and time to achieve the C max (T max ) were determined by using non-compartmental model. The 90% parametric confdence intervals (90% CI) values for the ratio of AUC 0-72 and C max of test/reference product were 101.3 (95.73-107.17) and 99.6 (92.50- 107.32), respectively. These values were within the acceptable range (80.00 – 125.00%). No adverse effect was observed during the study. The results of this study indicated that both formulation of ribavirin, Ribavirin GPO 400 mg tablets and Copegus ® 400 mg tablet were bioequivalent in term of rate and extent of drug absorption. Keyword: Ribavirin, Pharmacokinetics, Bioequivalence, Liquid chromatography tandem mass spectrometry 1. INTRODUCTION Ribavirin is a nucleoside analogue with exert an antiviral activity. The chemical name of ribavirin is 1-β-D-ribofuranosyl-1H- 1,2,4-triazole-3-carboxamide and chemical structure is shown in fgure 1. A broad spectrum antiviral activity of ribavirin have been suggested in several mechanism such as direct inhibition of viral RNA replication, inhibition of enzyme inosine-monophosphate-dehydrogenase (IMPDH), immunodulation, and mutagenesis 1, 2 . Ribavirin is absorbed rapidly following oral administration of a single dose of ribavirin (median Tmax = 1-2 hours). The absolute bioavailability is around 50%. Bioavailability of a single oral dose of ribavirin is increased to approximately 70% when co-administration with a high-fat meal. The mean half-life is 43.6 hours. The total apparent clearance following adminis- tration of a single oral dose is about 26 L/h 3 . In a single dose, randomized, open label, 2-way crossover bioequivalence study of Ribavirin 200 mg capsule in healthy subjects under fed condition, it revealed that C max of Ribavirin of test and reference were 582.133±17.044 ng/mL and 538.343±139.018 ng/mL, AUC 0-t were 6048.902±1343.191 ng.hr/mL and 6407.033± 1478.900 ng.hr/mL and T max were 1.783±0.709 hr and 2.325±0.496 hr, respectively 4 . *Corresponding author: E-mail address: isariya_t@gpo.or.th Original Article Mahidol Univ J Pharm Sci 2015; 42 (3), 118-125