目的 研究大黄酸(RH)iv给药后在大鼠血液和肾脏内的同步药动学行为以评价RH肾脏的渗透性.方法 应用HPLC法测定给药后大鼠血浆中RH质量浓度,经血浆蛋白结合率折算为血中游离药物浓度;采用微透析(MD)技术定时获取肾脏透析液,高效液相色谱-串联质谱(HPLC-MS/MS)技术测定大鼠肾脏透析液中RH的质量浓度;采用非房室模型拟合药动学参数.结果 给药后RH较快进入肾脏,在给药后1 h左右浓度达到峰值,其后持续下降,在给药后整个过程中,肾脏药物浓度均明显低于血液药物浓度.RH给药后在大鼠血液及肾脏中的平均滞留时间(MRT)分别为(87.217±29.889)、(122.387±12.521)min;药时曲线下面积(AUC)分别为(114.236±45.585)、(16.596±1.732)μg·min/mL,肾脏渗透率(AUC_肾脏/AUC_血液)为0.161±0.056.结论 大鼠血液/肾脏同步药动学研究是研究药物肾脏渗透性能的有效方法;RH iv给药后可有效地向肾脏渗透,从而有利于肾脏疾病的治疗.

Objective To investigate the pharmacokinetics of rhein (RH) in rat plasma and kidney simultaneously. Methods An HPLC method was developed to determine the concentration of RH in rat plasma, which was corrected with protein binding. Renal microdialysis (MD) technique was employed to collect dialysate sample continuously. Then the MD samples were detected by HPLC-MS/MS method. Results RH was distributed into kidney of rats rapidly after administration. The maximum concentration of RH in rat kidney was reached at 1 h followed by continuously decreased. During the whole process, the concentration of RH in rat kidney was significantly lower than that in plasma after administration. The MRT of RH in plasma and kidney was (87.217 ± 29.889) and (122.387 ± 12.521) min, respectively. The areas under the curve (AUC) of RH in plasma and kidney were (114.236 ± 45.585) and (16.596 ± 1.732) μg·min/mL, respectively. The kidney penetration was 0.161 ± 0.056. Conclusion Simultaneous pharmacokinetic study in rat plasma and kidney is an effective method to investigate drug kidney penetration. RH can penetrate rat's kidney after administration to exert its effect.

国家自然科学基金资助项目(81373982);浙江省自然科学基金资助项目(LY13H280007)