Pharmacokinetics and Tissue Distribution of Clevidipine and Its Metabolite in Dogs and Rats  

作　　者：周莹 何晓梦 李虎群 倪扬 许明珍 谌辉 黎维勇 

机构地区：[1]Institute of Clinic Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2014年第6期856-860,共5页华中科技大学学报（医学英德文版）

基　　金：supported in part by the Important National Science & Technology Specific Projects in the 12th Five-year Plan of China(No.2011ZX09302-002-01)

摘　　要：The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H 152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/（kg·min）, and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short （16.8 min）, pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/（min·kg）. In comparison, plasma concentra- tion of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the high- est concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small （0.042‰） compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite raoidlv.The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H 152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/（kg·min）, and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short （16.8 min）, pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/（min·kg）. In comparison, plasma concentra- tion of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the high- est concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small （0.042‰） compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite raoidlv.

关 键 词：PHARMACOKINETICS tissue distribution CLEVIDIPINE METABOLITE 

分 类 号：R965[医药卫生—药理学]