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目的:比较静脉注射9-硝基喜树碱内酯型与羧酸盐型溶液后大鼠体内药动学和肾排泄情况。方法:采用HPLC法同时测定大鼠血浆中9-硝基喜树碱内酯型浓度与总(内酯型+羧酸盐型)浓度以及尿液中9-硝基喜树碱的总浓度。按4mg.kg-1剂量给大鼠静脉注射9-硝基喜树碱内酯型与羧酸盐型溶液,绘制药-时曲线,并采用DAS 2.0软件拟合药动学参数。按同剂量给大鼠静脉注射9-硝基喜树碱内酯型与羧酸盐型溶液,并在各时间段收集尿液,测定尿液中9-硝基喜树碱原形药物累积排泄量。结果:根据AUC计算,9-硝基喜树碱内酯型与羧酸盐型溶液给药以后内酯型的比例分别为(46.7±8.0)%和(8.8±2.5)%,两者的MRT分别为(21.6±2.1)min与(12.7±5.1)min,Vz分别为(0.91±0.16)L.kg-1与(0.56±0.13)L.kg-1,t1/2分别为(17.2±2.4)min与(13.3±3.9)min,差异均有显著性,但总量的AUC并无明显差别。9-硝基喜树碱羧酸盐型及内酯型给药后累积尿液排泄百分率为(30.3±6.4)%和(8.9±0.8)%。结论:9-硝基喜树碱内酯型与羧酸盐型的体内药动学过程存在显著差异,羧酸盐型给药后的肾排泄量远高于内酯型。
OBJECTIVE: To compare the pharmacokinetics and renal excretion in rats after intravenous injection of 9-nitrocamptothecin and carboxylate solutions. Methods: Simultaneous determination of 9-nitrocamptothecin lactone and total (lactone + carboxylate) concentrations in rat plasma and total urinary 9-nitrocamptothecin concentrations were determined by HPLC. The rats were intravenously injected with 9-nitrocamptothecin type and carboxylate solution according to a dosage of 4 mg.kg-1, and the drug-time curve was drawn. The pharmacokinetic parameters were fitted by DAS 2.0 software. The rats were intravenously injected with 9-nitrocamptothecin lactone type and carboxylate solution at the same dose, urine was collected at various time points, and the cumulative excretion of 9-nitrocamptothecin in urine . Results: According to the AUC calculation, the ratio of lactone type in the 9-nitrocamptothecin and carboxylate solutions was (46.7 ± 8.0)% and (8.8 ± 2.5)%, respectively. The MRT (21.6 ± 2.1) min and (12.7 ± 5.1) min respectively, Vz was (0.91 ± 0.16) L.kg-1 and (0.56 ± 0.13) L.kg-1 respectively, and t1 / 2 was (17.2 ± 2.4 ) min and (13.3 ± 3.9) min, the differences were significant, but the total AUC did not differ significantly. The cumulative urine excretion rates after 9-nitrocamptothecin carboxylate and lactone administration were (30.3 ± 6.4)% and (8.9 ± 0.8)%, respectively. CONCLUSION: In vivo pharmacokinetics of 9-nitrocamptothecin and carboxylate are significantly different. The renal excretion after carboxylate administration is much higher than that of lactone.