西沙必利药代动力学研究

【作者】 傅军；

【导师】 熊玉卿；

【作者基本信息】 江西医学院 ， 药理学， 2001， 硕士

【摘要】 目的：1建立测定西沙必利血药浓度的高效液相色谱荧光检测法，研究国产西沙必利胶囊在中国健康志愿者体内的药代动力学特征及相对生物利用度。2探讨在联合用药情况下，奥美拉唑对西沙必利在兔体内药代动力学特征的影响。从而为西沙必利临床合理应用提供实验依据。方法：采用双周期交叉试验设计，12名健康志愿者随机分成两组，分别口服国产西沙必利片剂和胶囊15mg，一周后交叉。用高效液相色谱荧光检测法测定不同时间点血浆中西沙必利浓度，用3P97软件拟合房室模型，计算药代动力学参数并进行生物等效性评价。用高效液相色谱荧光检测法检测单独应用西沙必利及联合用药用药情况下（与奥美拉唑合用）的西沙必利血药浓度，用3P97软件拟合房室模型，计算药代动力学参数。结果：国产西沙必利胶囊和片剂的血药浓度-时间曲线符合二房室开放模型，其主要药代动力学参数：C_max分别为79.87±11.26和75.24±12.85μg/L，T_max分别为1.50±0.21和1.54±0.33h，AUC_0-36分别为777.05±128.47和771.61±129.01μg/L·h，T_（1/2）β分别为10.07+0.81和9.79+1.27h。国产西沙必利胶囊的相对生物利用度为101.12+9.89％。经方差分析和双单侧t检验，两制剂生物等效。兔单独用药组与联合用药组主要药代动力学参数：C_max分别为26.21±6.77和28.32±3.79μg/L，AUC_0-24分别为217.61+48.25和247.91+31.26μg/L·h，T_（1/2）β分别为8.30±0.67和8.81±0.50h，T_max均为0.92±0.17h。经t险验无显著性差异。结论：西沙必利血药浓度的高效液相色谱荧光检测法准确，灵敏，可靠。国产西沙必利胶囊与片剂生物等效。奥美拉唑对单次口服治疗量西沙必利在兔体内的药代动力学过程无显著性改变。更多还原

【Abstract】 Objective: 1. A HPLC-FLUOR method with detection was developed and validated to de ermine cisapride in plasma, to study the pharmacokinetics profile and bioequivalence of cispride in Chinese healthy volunteers. 2. To study the pharmacokinetics profiles of cisapride co ribined with omeprazole in rabbits. Methods: The study was conducted in a two-way cross-over design, as a single does randomized trial. Each volunteer was orally given cisapride tablet and capsule. Eight rabbits were divided into cispride group and in co ribination with omeprazole group. Plasma samples were assayed for cisapride using high- pe formance liquid chromatography method with fluorescence detection. The ph irmacokinetics pharmeters as well as relative bioavailability were measured. To compare the difference of two groups and realize the case of drugs interaction under the condition of co nbination with omeprazo]e. Results: the concentration-time curves of two formulations were conformed to a two-compartment open model with first-order absorption. The main phirmacokinetic pharmeters of capsule or tablet were as follows: ~ were 79.87?1.26 and 75.24?2.85 it gIL; Tmax were 1.50+0.21 and 1.54?.33 h; AUC036 were 777.05?28.47 and 77 1.61?29.01 it gIL h; T112~ were 10.07?.81 and 9.79?.27 h respectively. There were no significant difference between the two formulations (P>0.05). The relative bioavailability of cisapride capsule was 101.12?.89%. The pharmacokinetics parameters of single-does group and combination-does group of rabbits were as follow: ~ were 26.21?.77 and 28.32?.79 It g/L; AUC024 were 217.61+48.25 and 247.91?1.26 It gIL h; T112~ were 8.20+0.67 and 8.8 1?.50 h respectively; Tiiia~ were all 0.92?.17 h. There were no significant different between these parameters. Conclusion: A HPLC-FLUOR method that determine cuapride in plasma is sensitive, accurate and reliable. Domestic cisapride capsule and tablet were bioequivalent. The pharmacokinetics profiles of single-does cisapride will not be chtnged by co-administered omeprazole.更多还原