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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/m L,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 study synchronized pharmacokinetics of rat rheumatoid arthritis (RH) iv in rats’ blood and kidneys to evaluate the RH renal permeability. Methods The plasma concentration of RH in the rat plasma was determined by HPLC. The plasma protein binding rate was used to calculate the concentration of free drug in the blood. The dialysis fluid was obtained by dialysis on the basis of microdialysis (MD). The dialysis fluid was separated by high performance liquid chromatography-tandem mass spectrometry HPLC-MS / MS) was used to determine the mass concentration of RH in rat renal dialysate. The non-compartmental model was used to fit the pharmacokinetic parameters. Results After administration, RH quickly entered the kidney and peaked at about 1 h after administration, and continued to decrease afterwards. During the whole course of administration, the renal drug concentrations were significantly lower than those in blood. The mean retention time (MRT) in rat blood and kidneys after RH administration were (87.217 ± 29.889) and (122.387 ± 12.521) min, respectively. The AUCs were (114.236 ± 45.585) and 16.596 ± 1.732) μg · min / m L and renal permeability (AUC kidney / AUC blood) was 0.161 ± 0.056. Conclusions Synchronous pharmacokinetics of blood / kidneys in rats is an effective method to study the permeation of renal kidneys. RH iv can effectively penetrate the kidneys, which is beneficial to the treatment of renal diseases.