비소프롤올 제제의 생물학적 동등성 평가

Abstract

Bisoprolol, one of the 1-adrenorecepter antagonist, has been used for the treatment of mild to moderate essential hypertension and stable angina pectoris. The oral bioavailability of bisoprolol is high (90%) and the drug has a long elimination half-life, 9~12 hr, which allows once-daily administration. The bioequivalence of two bisoprolol preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Concor tablet made by Newgenpharm and the reference product was Monocor tablet made by Wyeth Korea. Twenty healthy male subjects, 23.8 (21-30) years old and 63.8(52-92) kg, were randomly divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 10 mg bisoprolol hemifumarate were orally administered, blood was taken at predetermined time intervals and the concentration of bisoprolol in plasma was determined using an HPLC method with fluorescence detector. Two pharmacokinetic parameters, AUCt and Cmax were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of AUCt and Cmax were log 0.95~log 1.04 and log 0.96~log 1.07, respectively. These values were within the acceptable bioequivalence intervals of log 0.8~log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Concor tablet is bioequivalent to Monocor tablet.