프레팔시드 정(시사프리드 5 mg)에 대한 시사플 정의 생물학적 동등성

Bioequivalence of Prepulsid Tablet to Cisaple Tablet (Cisapride 5 mg)

Bioequivalence of two cisapride tablets, test drug ($Cisple^{\circledR}$ tablet: Hanmi Pharm Co., Ltd.) and reference drug ($Prepulsid^{\circledR}$ tablet: Janssen Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty two healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a $2{\times}2$ crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. $AUC_{0-36hr}$ (area under the plasma concentration-time curve from time zero to 36 hr), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 5.38, 6.17 and 0.00% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The powers $(1-\beta)$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ were over 0.9. Minimal detectable differences $(\Delta)$ at ${\alpha}=0.05,\;1-{\beta}=0.8$ were less than 20% (i.e. 17.67, 14.84 and 19.72% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The 90% confidence intervals $(\delta)$ for these parameters were also within ${\pm}20%$ $(i.e.\;-4.97\;{\le}{\delta}{\le}\;15.73,\;-2.53{\le}{\delta}{\le}\;14.86\;and\;-11.55{\le}{\delta}{\le}\;11.55$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.