西沙必利片剂和胶囊剂人体药代动力学及相对生物利用度研究

摘要

OBJECTIVE：To study the pharmacokinetics and relative bioavailability of cisapride tablets and capsules in health volunteers.METHOD:In a randomized crossover study,single oral dose(15mg) of cisapride tablets,capsules and its contrast tablets were administered to 12 healthy volunteers.Plasma cispride concentration were determined by high-performance liquid chromatography.RESULTS:The main pharmacokinetic parameters of sample tablets were Tpeak=1.20±0.50h,t1/2β=9.12±1.79h,Cmax=68.52±9.26μg*h*L-1,AUC0～∞=491.6±108.8μg*h*L-1,sample capsules were Tpeak=1.29±0.50h,t1/2β=8.34±1.44h,Cmax=68.61±10.96μg*h*L-1,AUC0～∞=498.0±127.57μg*h*L-1,contrast tablets were Tpeak=1.45±0.55h,t1/2β=9.26±2.84h,Cmax=62.52±9.87μg*h*L-1,AUC0～∞=476.67±105.11μg*h*L-1.CONCLUSION:There is no significant difference of AUC0～∞ and Cmax among sample tablets,capsules and contrast tablets(P＞0.05).Tpeak of sample tablets and capsules were shorter(P＜0.05) than that of contrast tablets.The relative bioavailability of the cispride tablets was 103.99%±11.97%,the capsules was 104.40%±15.15%.%目的：研究西沙必利片剂及胶囊剂在健康人体内的药代动力学及相对生物利用度。方法：采用反相高效液相色谱法测定12名健康自愿者单剂量口服三种制剂各15mg后，血浆中西沙必利浓度变化情况，用3P97程序按非室模型进行药代动力学分析。结果：测得主要药代动力学参数为：试验片剂Tpeak=1.20±0.50h,t1/2β=9.12±1.79h,Cmax=68.52±9.26μg*h*L-1,AUC0～∞=491.6±108.8μg*h*L-1,AUC0～36=475.9±104.9μg*h*L-1;试验胶囊剂Tpeak=1.29±0.50h,t1/2β=8.34±1.44h,Cmax=68.61±10.96μg,AUC0～∞=498.0±127.6μg*h*L-1,AUC0～36=483.6±124.1μg*h*L-1;对照片剂Tpeak=1.45±0.55h,t1/2β=9.26±2.84h,Cmax=62.52±9.87μg*h*L-1,AUC0～∞=476.67±105.11μg*h*L-1,AUC0～36=426.6±100.7μg*h*L-1。结论：经生物等效性分析，试验片剂和胶囊剂与对照片剂相比吸收较快(P＜0.05)；AUC0～∞、AUC0～36、Cmax均与对照片剂生物等效(P＞0.05)；片剂、胶囊剂与对照片剂的相对生物利用度F0～∞分别为104.0%±12.0%和104.4%±15.2%，F0～36分别为103.7%±12.1%和104.0%±14.4%。