Effect of Rutin Combined with Nimodipine on the Pharmacokinetics of Nimodipine
LATIN AMERICAN JOURNAL OF PHARMACY(2021)
摘要
Through in vivo and in vitro experiments, the pharmacokinetic interaction of rutin with nimodipine was studied. The pharmacokinetic of nimodipine (25 mg/kg) with or without rutin (20 mg/kg/day) was studied. Meanwhile, the transport and metabolic stability of nimodipine was studied in the Caco-2 model and rat liver microsomes. Rutin dramatically suppressed the C-max (22.41 +/- 1.93 vs. 36.55 +/- 6.87 ng/mL) and t(1/2) (from 4.13 +/- 0.30 to 2.65 +/- 0.17 h) of nimodipine. The efflux ratio of nimodipine was significantly increased from 1.56 to 1.93. Moreover, the metabolic stability of nimodipine was significantly increased with the intrinsic clearance rate increased from 36.69 +/- 1.71 to 50.66 +/- 2.31 mu L/min/mg protein by rutin. The in vivo pharmacokinetic study showed a decrease in the system exposure of nimodipine, which might be the results of the inducing of CYP3A4 and P-gp activity by rutin.
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关键词
CYP3A4,Drug-drug interaction,Nimodipine,P-gp,Rutin
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