CN: 32-1845/R
ISSN: 2095-6975
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PARK Ji-Won, CHOI Jin-Seok. Role of kaempferol to increase bioavailability and pharmacokinetics of nifedipine in rats[J]. Chinese Journal of Natural Medicines, 2019, 17(9): 690-697

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

PARK Ji-Won1, CHOI Jin-Seok2
1 Hazardous Substances Analysis Division, Gwangju Regional Office of Food and Drug Safety, Gwangju 61012, Republic of Ko-rea;
2 Department of Medical Management, Chodang University, Jeollanam-do 58530, Republic of Korea
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 dehy-dronifedipine 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.
Key words:    Nifedipine    Kaempferol    CYP3A4    P-gp    Pharmacokinetics    Bioavailability   
Received: 2019-04-16   Revised:
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