盐酸氯苯胍在兔体内的药动学及生物利用度研究

【目的】研究抗球虫药盐酸氯苯胍在家兔体内的药物代谢动力学特征及内服给药的生物利用度。【方法】16只健康新西兰大白兔,公母各半,分为2组,一组以2.00 mg·kg~(-1)单次静脉注射给药,另一组以100.00 mg·kg~(-1)单次内服给药,通过耳部静脉采血,并用HPLC-UV法检测血浆中的盐酸氯苯胍浓度。使用WinnonlinTM药动学软件非房室模型计算相关药动学参数,采用SPSS 16.0软件得到药时曲线图。【结果】兔静脉注射盐酸氯苯胍(2.00mg·kg~(-1))后,药-时曲线下面积为1.72μg·h·m L~(-1),血浆清除率为1.17 L·h~(-1)·kg~(-1),表观分布容积为2.87L·kg~(-1),消除半衰期为1.72 h;内服盐酸氯苯胍(100.00 mg·kg~(-1))后,药-时曲线下面积为6.33μg·h·m L~(-1),消除半衰期为8.94 h。盐酸氯苯胍2种给药方式的药动学参数均存在显著差异(P0.05),内服给药的生物利用度较低,仅为7.36%。【结论】盐酸氯苯胍静脉注射给药的表观分布容积较大,药物在兔组织中分布广泛,并且消除迅速;内服盐酸氯苯胍后,药物经肠道吸收的量较少,体内药物残留较低。

Studies on pharmacokinetic and bioavailability of robenidine hydrochloride in rabbits

[Objective] To investigate the pharmacokinetics and bioavailability after oral administration of the coccidiostat , robenidine hydrochloride in rabbits .[Method] A total of 16 healthy New Zealand white rabbits were allotted to two groups and received single intravenous administration of robenidine hydrochlo -ride at the dose of 2.00 mg· kg -1 and single oral administration at the dose of 100.00 mg· kg -1 respec-tively.Blood samples were collected and analyzed by high-performance liquid chromatography ( HPLC) using UV.Pharmacokinetic parameters were estimated using the Winnonlin TM software package and the curve of time and concentration was obtained using SPSS 16.0.[Result]After i.v.injection, area under the concentration-time curve ( AUC ) was 1.72 μg · h · mL-1 , plasma clearance ( CI ) was 1.17 L· h-1 · kg -1 , the volume of distribution was 2.87 L· kg -1 and the half-life of elimination ( t1/2 ) was 1.72 h.After oral administration , t1/2 was 8.94 h and AUC was 6.33μg· h· mL-1 .Statistical analysis showed that there were significant differences between pharmacokinetic parameters of intravenous and oral administration ( P <0.05 ) , and the bioavailability following oral administration was low ( 7.36%) .[Conclusion]The volume of distribution following robenidine hydrochloride was high , suggesting that the drug was widely distributed in rabbits and eliminated rapidly;Robenidine hydrochloride for oral adminis-tration was rarely absorbed into the blood or blood circulation , and the residues in vivo was low .