Role of kaempferol to increase bioavailability and pharmacokinetics of nifedipine in rats  

作　　者：PARK Ji-Won CHOI Jin-Seok 

机构地区：[1]Hazardous Substances Analysis Division,Gwangju Regional Office of Food and Drug Safety,Gwangju 61012,Republic of Korea [2]Department of Medical Management,Chodang University,Jeollanam-do 58530,Republic of Korea

出　　处：《Chinese Journal of Natural Medicines》2019年第9期690-697,共8页中国天然药物（英文版）

摘　　要：Herein,the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats.The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats.Moreover,the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats.The in vitro studies of kaempferol were investigated on P-glycoprotein(P-gp)and cytochrome P450(CYP)3A4 activity.Kaempferol reduced a 50%inhibitory concentration(IC50)of 8.6μmol·L-1 on CYP3A4 enzyme activity.Moreover,kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp.Depending on increased concentrations of kaempferol,the areas under the plasma concentration–time curve(AUC0-∞)and the peak concentration(Cmax)of nifedipine were increased after oral and intravenous administration.Moreover,the absolute bioavailability(AB)and relative bioavailability(RB)of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration.Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver,or both.Herein, the purpose of this study is to evaluate the effects of kaempferol on bioavailability and pharmacokinetics of nifedipine and its metabolite dehydronifedipine in rats. The experimental design is based on with or without kaempferol in the oral and intravenous administration of nifedipine in rats. Moreover, the pharmacokinetic parameters including nifedipine and dehydronifedipine were evaluated in rats. The in vitro studies of kaempferol were investigated on P-glycoprotein（P-gp） and cytochrome P450（CYP）3A4 activity. Kaempferol reduced a 50% inhibitory concentration(IC50) of 8.6 μmol·L-1 on CYP3A4 enzyme activity. Moreover, kaempferol clearly improved the cell internalization of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Depending on increased concentrations of kaempferol, the areas under the plasma concentration–time curve(AUC0-∞) and the peak concentration（Cmax） of nifedipine were increased after oral and intravenous administration. Moreover, the absolute bioavailability（AB） and relative bioavailability（RB） of nifedipine in the presence of kaempferol was significantly higher than those of the control group after oral and intravenous administration. Improvement of bioavailability of nifedipine by kaempferol may be mainly because of the inhibition of the P-gp-mediated efflux transporter in the small intestine and CYP3A4-mediated metabolism in the small intestine or liver, or both.

关 键 词：NIFEDIPINE KAEMPFEROL CYP3A4 P-GP PHARMACOKINETICS BIOAVAILABILITY 

分 类 号：R969.1[医药卫生—药理学]