[关键词]
[摘要]
目的 比较复方五仁醇胶囊（CWC）和五酯胶囊（WZC）及CWC单次和长期给药对他克莫司（FK506）在大鼠体内药动学的影响。方法 24只大鼠随机分成FK506组、CWC+FK506组、WZC+FK506组和CWC7d+FK506组，每组6只。FK506组、CWC+FK506组和WZC+FK506组分别一次性ig给予FK506、CWC+FK506、WZC+FK506，CWC7d+FK506组前6 d连续ig给予CWC，第7天ig给予CWC和FK506。各组大鼠于给药前和给药后不同时间点（CWC7d+FK506组为末次给药前后）眼眶取血，测定FK506血药浓度，计算FK506主要药动学参数。结果 与FK506组比较，WZC+FK506组和CWC+FK506组大鼠FK506血药浓度峰值（Cmax）明显提高（P<0.05、0.01），药-时曲线下面积（AUC0~t）显著增加（P<0.01），体内滞留时间（MRT0~t）明显延长（P<0.05、0.01），表观分布容积（V/F）及药物消除率（CL/F）显著减少（P<0.01）；与WZC+FK506组比较，CWC+FK506组大鼠FK506 AUC0~t显著增加（P<0.01），CL/F明显减少（P<0.05）。与CWC+FK506组比较，CWC7d+FK506组大鼠FK506 Cmax显著提高（P<0.01），血药浓度达峰时间（tmax）明显缩短（P<0.05），AUC0~t明显增加（P<0.05），CL/F明显减少（P<0.05）。结论 CWC和WZC均可提高FK506 Cmax，增加AUC0~t，延长MRT0~t，减小V/F和CL/F；在增加FK506 AUC0~t、减少CL/F方面，CWC优于WZC；在提高Cmax、增加AUC0~t、缩短tmax方面，CWC长期给药优于单次给药。
[Key word]
[Abstract]
Objective To compare the effect of Compound Wurenchun Capsule (CWC) and Wuzhi Capsule (WZC), CWC single and long-term administration on the pharmacokinetics of tacrolimus (FK506). Methods Twenty-four rats were randomly divided into FK506, CWC + FK506, WZC + FK506 and CWC7d + FK506 groups, with six rats in each group. Rats in FK506, CWC + FK506, and WZC + FK506 groups were given a single gavage with FK506, CWC + FK506, and WZC + FK506 respectively. Rats in CWC7d + FK506 group was given a multiple gavage regimen of daily CWC gavage for 6 d, CWC and FK506 on day 7. Blood sample from orbit before and after gavage at different time points (CWC7d + FK506 group before and after the last administration) were tested for FK506 blood concentration and the pharmacokinetic parameters were calculated. Results Compared with FK506 group, peak blood concentration (Cmax) and area under the curve (AUC0-t) of FK506 increased significantly (P < 0.05, 0.01), body retention time (MRT0-t) of FK506 prolonged significantly (P < 0.05, 0.01), the apparent volume of distribution (V/F) and the drug elimination rate (CL/F) of FK506 decreased significantly (P < 0.01) in WZC + FK506 and CWC + FK506 groups. Compared with WZC + FK506 group, AUC0-t of FK506 increased significantly (P < 0.01), CL/F of FK506 decreased significantly (P < 0.01) in CWC + FK506 group. Compared with CWC + FK506 group, Cmax of FK506 increased significantly (P < 0.01), time to peak blood concentration (tmax) of FK506 shortened significantly (P < 0.05), AUC0-t of FK506 increased significantly (P < 0.05), CL/F of FK506 decreased significantly (P < 0.05) in CWC7d + FK506 group. Conclusion Both CWC and WZC can increase Cmax and AUC0-t, prolong MRT0-t, reduce V/F and CL/F of FK506. CWC is better than WZC in increasing AUC0-t and inhibiting CL/F of FK506. CWC long-term administration is better than single-dose in improving Cmax, AUC0-t and reducing tmax of FK506.
[中图分类号]
[基金项目]
南通市关键技术研究项目（MS22015086）；江苏省药学会Shire生物药学基金课题（S201608）；南通市科技计划项目（YYZ16017）；南通市卫生计生委青年医学人才科研基金项目（WQ2016017）
