簡介：
臨床療效變異部份原因可能是藥品代謝酵素之活性差異所造成。因此，以探針性藥物來評估體內酵素活性有利於控制藥效上之變異。胃腸蠕動促進劑 cisapride 主要經由 CYP3A 代謝且其並非為 p-glycoprotein 之受質。最近文獻指出 cisapride單一口服劑量給與後八小時之血漿濃度可預測其清除率，並以 cisapride 作為探針性試藥來評估人體體內 CYP3A 活性。

研究目的：
本研究目的在探討使用 cisapride 靜脈注射給藥後之單一血漿濃度作為在大白鼠體內CYP3A探針性試藥之可行性。

研究方法：
在控制組大白鼠給與cisapride 1, 3, 5, 7.5, 10 mg/kg。而在 CYP3A 活性調整之試驗組別，經由 dexamethasone (誘導), ketoconazole (抑制)或 erythromycin (抑制) 之預處理後給與 5 mg/kg 之 cisapride。Cisapride 之血漿濃度定量至 480 分鐘，其藥物動力學參數經由非室模式來估算。另外，在大白鼠肝臟微粒體之 CY3A2 含量則以西方點墨法來測量。

研究結果：
劑量 1, 3, 5, 7.5, 10 mg/kg 之控制組的血中濃度曲線下面積 (AUC) 與血中濃度最佳之相關性，分別在 150, 40, 40, 150, 150 分鐘。至於在CYP3A 活性調整之試驗組別中，無論誘導組或抑制組其最佳之相關性皆在 40 分鐘。若綜合各個組別之數據，則其最佳之相關性在 90 分鐘。而大白鼠之肝臟 CYP3A2 含量與 cisapride 之 AUC 亦有線性之相關性。

研究結論：
大白鼠靜脈注射 cisapride 後 90 分鐘之單點血中濃度可以預測其血中濃度曲線下面積以及其清除率。顯示 cisapride 單點法為評估體內 CYP3A 活性之有效方法。

Introduction. Variability in drug response can be attributed in part to variability in the activity of drug-metabolizing enzymes. Measuring in vivo enzyme activity by probe drugs can therefore provide valuable information for managing variability in drug response. The prokinetic agent cisapride is metabolized primarily by CYP3A and it is not a substrate of Pgp. The applicability of cisapride as a probe substrate to assess in vivo CYP3A activity in humans has been demonstrated recently. And the 8-hr plasma concentration of cisapride after a single oral dose has been served as a predictor of its clearance.

Purpose. In this study, the applicability of a single cisapride plasma concentration as in vivo probe for CYP3A in rats was investigated following intravenous administration of cisapride.

Methods. Rats received cisapride (1, 3, 5, 7.5 or 10 mg/kg) in the dose-linearity control groups. And in the CYP3A modulation groups, rats received 5 mg/kg cisapride after pretreatment with dexamethasone (induction), ketoconazole (inhibition), or erythromycin (inhibition). The plasma concentrations of cisapride were followed for 480 min, and the kinetic parameters were estimated by non-compartmental analysis. The contents of CYP3A2 in hepatic microsomes of rats were measured by western blotting analysis.

Results. Optimal correlations between area under concentration-time curve (AUC) and plasma concentration in the control groups were at 150, 40, 40, 150, and 150 min for the 1, 3, 5, 7.5 or 10 mg/kg dosing groups, respectively. In the CYP3A modulation groups, correlation for the induction and inhibition groups were both optimal at 40 min. In the composite analysis of all treatments, optimal correlation occurred at 90 min. The hepatic CYP3A2 contents of rats also showed linear correlation with cisapride AUC.

Conclusion. A single 90-min plasma concentration following intravenous administration of cisapride can predict its AUC and hence clearance in rats. Therefore, this approach represents an effective method for assessing in vivo CYP3A activity.

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楊淑珍，體外 CYP3A 活性探針性試藥之開發：Cisapride 與Delavirdine，國立成功大學臨床藥學研究所碩士論文，九十三學年度。

黃千真，以 Midazolam 在老鼠之代謝酵素動力學探討 Ursodeoxycholic Acid 對細胞色素 3A 藥物代謝之影響，國立成功大學臨床藥學研究所碩士論文，九十一學年度。