Abrudan Maria Bianca, Muntean Dana Maria, Gheldiu Ana Maria, Neag Maria Adriana, Vlase Laurian
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hațieganu", Faculty of Medicine, Cluj-Napoca, Romania.
Pharmacology. 2017;99(3-4):139-143. doi: 10.1159/000453619. Epub 2017 Jan 5.
BACKGROUND/AIMS: The effects of multiple-dose bupropion on the pharmacokinetics of single-dose carvedilol were investigated in order to evaluate this possible drug-drug interaction.
A preclinical study was conducted among white male Wistar rats. Each rat was cannulated on the femoral vein prior to being connected to BASi Culex ABC®. During the reference period, each rat received an intravenous and an oral dose of 3.57 mg/kg body weight (b.w.) carvedilol, at 2 days distance. After 5 days of pretreatment with 21.42 mg/kg b.w. bupropion (by oral route, twice a day - given in order to reach the steady state), during the sixth day, 3.57 mg/kg b.w. carvedilol and 21.42 mg/kg b.w. bupropion were orally co-administrated (test period). After each administration of carvedilol, several samples of 200 µL blood were collected. The pharmacokinetic parameters of carvedilol were analyzed by the noncompartmental method.
The 5 days pretreatment with bupropion increased the exposure to carvedilol in rats by 180%, considering the modifications observed in the area under the curve of carvedilol. Carvedilol was shown to have higher plasma concentrations, delay in maximum concentration, and a prolonged half-life, after being pretreated with bupropion.
The administration of multiple-dose bupropion influences the pharmacokinetics of carvedilol (single oral dose) in rats.
背景/目的：研究多剂量安非他酮对单剂量卡维地洛药代动力学的影响，以评估这种可能的药物相互作用。
在雄性白色Wistar大鼠中进行了一项临床前研究。每只大鼠在连接到BASi Culex ABC®之前，先进行股静脉插管。在参考期内，每只大鼠在相隔2天的时间接受静脉注射和口服3.57mg/kg体重的卡维地洛。在用21.42mg/kg体重的安非他酮（经口服途径，每天两次，以达到稳态）预处理5天后，在第6天，口服联合给予3.57mg/kg体重的卡维地洛和21.42mg/kg体重的安非他酮（试验期）。每次给予卡维地洛后，采集几份200μL血液样本。采用非房室模型方法分析卡维地洛的药代动力学参数。
考虑到卡维地洛曲线下面积的变化，安非他酮预处理5天使大鼠体内卡维地洛的暴露量增加了180%。经安非他酮预处理后，卡维地洛的血浆浓度更高，达峰浓度延迟，半衰期延长。
多剂量安非他酮的给药影响大鼠体内卡维地洛（单次口服剂量）的药代动力学。
