A Comparative Bioavailability Study on Two Brands of Cisapride Tablets Using Univariate and Multivariate Statistical Methods
Ju-Yu Hsu1, Mei-Yu Hsu2, Hsing-Chu Hsu3*, Chang-Sha Lu4, Cho-Fu Wang4, Pon-Chuan Chen5 and Chung-Lung Lu5
1. Sidney Kimmel Cancer Center, 10835, Altman Row, Suite 240, San Diego, CA 92121, U.S.A.
2. The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4268, U.S.A.
3. Chia Nan College of Pharmacy and Science, 60, Al-jen Rd., Sect. 1, Pau-an, Jen-teh hsiang, Tainan hsien, Taiwan
4. Swiss Pharmaceutical Company, 164, Su-wei Street, Yong-kang City, Tainan hsien, Taiwan
5. Sin-Lau Christian Hospital, 57, Tong-mung Rd., Sect. 1, Tainan City, Taiwan.
ABSTRACT
A comparative bioavailability study on the original inventor's (Prepulsid, Janssen) and a generic (Cisapride, Swiss Pharm. Taiwan) cisapride tablets was carried out using a single dose, 2x2 randomized crossover design with 16 normal Chinese males. The pharmacokinetic parameters of cisapride obtained following oral administration of 20 mg dose of Prepulsid and Cisapride tablets were Cmax (61.97±13.11 and 64.89±14.31 ng/ml, mean±SD), partial AUC (AUCt, 402±121.4 and 405.4±117.5 ng.h/ml), total AUC (420.8 ±123.8 and 421.9±118.0 ng .h/ml), T1/2 (7.8±1.9 and 7.2±1.8 h), Tmax (1.3±0.5 and 1.2±0.5 h), MRT (8.5±1.7 and 8.1±1.4 h), VRT (102.0±42.6 and 87.4±41.3 h2) and Cl/F (853.1±238.9 and 850.4±240.7 ml/min), respectively. The bioavailability parameters (Cmax, AUCt, AUC, lnCmax, lnAUCt and lnAUC) were analyzed by univariate statistical methods of the power of test to detect a 20% difference, 90% confidence interval, FDA's two one-sided tests and 90% joint confidence region. The results show that the two brands of cisapride tablet are bioequivalent based on current bioequivalence criteria. Overall similarity in bioavailability between the two products determined by multivariate statistical method was 94% (Cmax and AUC) and 92% (lnCmax and lnAUC); whereas overall similarity was 86% (Cmax, AUC and MRT) and 76% (lnCmax, lnAUC and lnMRT), respectively. The Tmax obtained in this study was comparable to that reported in Caucasian subjects, but Cmax and AUC were smaller in Chinese.
Key words :cisapride, tablets,Chinese, bioavailability, multivariate analysis