新型蒽环类衍生物HYY-014大鼠体内药代动力学和组织分布的研究

目的：研究新型蒽环类衍生物HYY-014在大鼠体内的药代动力学和组织分布特征，为临床研究提供实验依据。方法大鼠单次尾静脉注射1．5 mg/kg的HYY-014后，采用LC-MS/MS法测定各时间点血浆和组织中HYY-014及其代谢物HYY-M3的浓度，药代动力学参数经DAS 3．0统计软件计算获得。结果采用统计矩方法处理药物浓度时间数据， HYY-014药代动力学参数 Cmax、T1/2、Vd、CL、AUC0-t、MRT0-t分别为(1628．6±618．6)μg/L、(24．4±3．6) h、(23．4±5．2) L/kg、(0．66±0．08) L/kg/h、(2219．5±276．9)μg/L ·h、(15．1±2．4) h；HYY-M3药代动力学参数Cmax、AUC0-t分别为(2．2±0．6)μg/L、(103．1±13．7)μg/L·h。静脉注射该药后，很快向机体的各组织广泛分布，且具有明显的靶向性，主要分布在脾、肾、肺、心脏、肝等组织，脑组织中浓度极低。结论静脉注射HYY-014组织分布广泛，具有明显的靶向性，肺、肝组织中的药物浓度均较高，不能通过血脑屏障。

Pharmacokinetic and tissue distribution studies of HYY-014, a novel derivate of anthracycline

Objective To study the pharmacokinetics and tissue distribution on HYY-014 , a novel derivate anthra-cycline. Methods The plasma and tissues concentrations of HYY-014 and HYY-M3 were detected by LC-MS/MS method after intravenous administration of 1 . 5 mg/kg HYY-014 . The pharmacokinetic parameters were calculated by the procedure of DAS 3. 0. Results The concentration-time data were analyzed by statistical moment principle. The pharmacokinetic parameters Cmax, T1/2, V, CL, AUC0-t and MRT0-t of HYY-014 were(1 628. 6 ± 618. 6) μg/L, (24. 4 ± 3. 6) h, (23. 4 ± 5. 2) L/kg, (0. 66 ± 0. 08) L/kg/h, (2 219. 5 ± 276. 9) μg/L·h, (15. 1 ± 2. 4) h. The pharmacokinetic parameters Cmax and AUC0-t of HYY-M3 were (2. 2 ± 0. 6) μg/L, (103. 1 ± 13. 7) μg/L ·h. After administrated intravenously, HYY-014 was quickly distributed to the body widely, the target organs were spleen, kidney, lung, heart and liver. The concentration of the brain was very low. Conclusion The distri-bution of HYY-014 is higher in lung and liver after administrated intravenously. It can’ t permeate blood brain bar-rier.