盐酸双苯氟嗪在Beagle犬体内的药代动力学

Pharmacokinetics of dipfluzine hydrochloride in Beagle dogs after single intravenous dose

目的研究新型钙通道阻断剂盐酸双苯氟嗪在Beagle犬的药代动力学。方法Beagle犬18只,随机分为低、中、高3个剂量组,分别单次股静脉注射1.5、3.0和6.0 mg.kg-1的盐酸双苯氟嗪溶液,后肢股静脉分时取血,处理,反相高效液相法(RP-HPLC)测定血浆中盐酸双苯氟嗪的浓度,应用3P97软件计算主要药代动力学参数。结果所建立测定方法的特异性、最低检测限、最低定量限、提取回收率、日内和日间精密度及稳定性均符合药代动力学分析方法的要求。单次静脉注射后,盐酸双苯氟嗪在Beagle犬体内的药代动力学过程符合开放二房室模型,低、中、高3个剂量的主要药代动力学参数:T12β分别为24.7、24.2和29.6 h;AUC分别为0.44、1.12和2.86 g.min.L-1;Vc分别为1.30、1.22和1.28 L.kg-1;CL分别为3.4×10-3、2.7×10-3和2.1×10-3L.kg-1.min-1。结论本研究建立的RP-HPLC法能够满足盐酸双苯氟嗪药代动力学研究的要求,静脉注射盐酸双苯氟嗪在犬体内消除过程属于两相消除,AUC与剂量呈线性相关。

Aim To investigate the pharmacokinetics of dipfluzine hydrochloride, a novel piperazines calcium antagonist. Methods Eighteen Beagle dogs were randomly divided into three groups, which were administered with dipfluzine hydrochloride at iv single dose of 1.5, 3.0 and 6.0 mg·kg^-1, respectively. The blood was collected at different time. A RP-HPLC method was developed to determine the concentration of dipfluzine hydrochloride in plasma. The pharmacokinetic parameters were calculated by 31997 software, Results The specificity, lowest limit of detection and quantification, extraction recoveries, the precision of intra- and inter-day and stability were qualified to the pharmacokinetic study. The concentration-time courses of dipfluzine hydrochloride were best fitted to a two-compartment open model at three doses. The main pharma-cokinetic parameters at three doses were 24. 7, 24. 2 and 29. 6 h for T12β, 0.44, 1.12 and 2.86 g·min·L^-1 for AUC, 1.30, 1.22 and 1.28 L·kg^-1 for Vc, and 3.4×10^-3, 2.7×10^-3 and 2.1×10^-3 L·kg^-1·min^-1 for CL, respectively. Conclusions The developed RP-HPLC method for determination of dipfluzine hydroehloride in plasma can satisfy the requirement of pharmaeokinetie study after iv dipfluzine hydrochloride. Analysis of plasma concentration-time curves indicates a biphasic decrease. There was a linear relationship between AUC and dosage.