Bioequivalence of Torad tablet 5 mg to Torem tablet 5 mg (torasemide 5 mg)

Abstract

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem (Roche Korea Co., Ltd., Korea, reference drug) and Torad (Samchundang Pharmaceutical Co., Ltd., Korea, test drug) tablet, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-eight healthy male Korean volunteers, 23.68 ± 1.79 years in age and 67.59 ± 9.87 kg in body weight, were divided into two groups and received each medicine at the torasemide dose of 10 mg in a randomized 2 × 2 crossover study. After a single administration, blood samples were taken at predetermined time intervals and the serum concentrations of torasemide were monitored by an HPLC–UV. The in vitro dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUC_t (the area under the serum concentration–time curve from time zero to 12 h), C_max (maximum serum drug concentration), and T_max (time to reach C_max) were calculated, and computer programs (equiv test and K-BE test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed AUC_t and C_max. The results showed that the differences between two formulation based on the reference drug, −2.84, −1.22 and 15.91 % for AUC_t, C_max, and T_max, respectively. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90 % confidence intervals using logarithmically transformed data were within the acceptance range of log0.80 to log1.25 (e.g., log0.9305−log1.0043 and log0.9422−log1.0903 for AUC_t and C_max, respectively). Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Torad tablet and Torem tablet are bioequivalent.