以單變項和多變項統計解析法檢定二種廠牌的Cisapride錠劑之生體可用率   全文下載

A Comparative Bioavailability Study on Two Brands of Cisapride Tablets Using Univariate and Multivariate Statistical Methods

本文報告原開發廠Janssen公司之Prepulsid和瑞士藥廠之學名藥品cisapride錠劑口服後之相對性生體可用率。以單劑量（20mg）交叉試驗方式使用16名健康男性進行試驗。其血漿藥物動力學參數值（prepulsid和cisapride）分別為：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）單變項統計解析之結果，皆符合現行生體相等性規定，故二種廠牌之cisapride錠劑具生體相等性。多變項統計解析得知，若同時評估Cmax 及AUC，二產品之生體可用率類同度為94%，同時評估lnCmax 及lnAUC，類同度為92%。若同時評估Cmax，AUC和MRT，則類同度為86%，若同時評估lnCmax，lnAUC和lnMRT，則類同度為76% 。華人和白種人服藥後之Tmax無差異，但華人之Cmax及AUC比白種人低。"

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 (AUCb 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), T112 (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 CI/F (853.1 ± 238.9 and 850.4 ± 240.7 ml/min), respectively. The bioavailability parameters (Cmax, AUCb 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% (lnCmaxand lnAUC); whereas overall similarity was 86% (Cmax, AUC and MRT) and 76% (lnCmax, lnAUC and lnMRT), respectively. The T max obtained in this study was comparable to that reported in Caucasian subjects, but Cmax and AUC were smaller in Chinese. 本文報告原開發廠Janssen公司之Prepulsid和瑞士藥廠之學名藥品cisapride錠劑口服後之相對性生體可用率。以單劑量（20mg）交叉試驗方式使用16名健康男性進行試驗。其血漿藥物動力學參數值（prepulsid和cisapride）分別為：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）單變項統計解析之結果，皆符合現行生體相等性規定，故二種廠牌之cisapride錠劑具生體相等性。多變項統計解析得知，若同時評估Cmax 及AUC，二產品之生體可用率類同度為94%，同時評估lnCmax 及lnAUC，類同度為92%。若同時評估Cmax，AUC和MRT，則類同度為86%，若同時評估lnCmax，lnAUC和lnMRT，則類同度為76% 。華人和白種人服藥後之Tmax無差異，但華人之Cmax及AUC比白種人低。