کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2010774 1066988 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of nifedipine on the pharmacokinetics of repaglinide in rats: Possible role of CYP3A4 and P-glycoprotein inhibition by nifedipine
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Effects of nifedipine on the pharmacokinetics of repaglinide in rats: Possible role of CYP3A4 and P-glycoprotein inhibition by nifedipine
چکیده انگلیسی

BackgroundThe aim of this study was to investigate the effects of nifedipine on the bioavailability and pharmacokinetics of repaglinide in rats.MethodsThe effect of nifedipine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. The pharmacokinetic parameters of repaglinide and blood glucose concentrations were also determined in rats after oral (0.5 mg/kg) and intravenous (0.2 mg/kg) administration of repaglinide to rats in the presence and absence of nifedipine (1 and 3 mg/kg).ResultsAdministration of nifedipine resulted in inhibition CYP3A4 activity with an IC50 value of 7.8 μM, and nifedipine significantly inhibited P-gp activity in a concentration-dependent manner. Compared to the oral control group, nifedipine significantly increased the area under the plasma concentration-time curve (AUC0–∞) and the peak plasma concentration (Cmax) of repaglinide by 49.3 and 25.5%, respectively. Nifedipine significantly decreased the total body clearance (CL/F) of repaglinide by 22.0% compared to the oral control group. Nifedipine also increased the absolute bioavailability (AB) of repaglinide by 50.0% compared to the oral control group (33.6%). In addition, the relative bioavailability (RB) of repaglinide was 1.16- to 1.49-fold greater than that of the control group. Compared to the intravenous control, nifedipine significantly increased AUC0–∞ of repaglinide. Blood glucose concentrations had significant differences compared to the oral control groups.ConclusionNifedipine enhanced the oral bioavailability of repaglinide, which may be mainly attributable to inhibition of CYP3A4-mediated metabolism of repaglinide in the small intestine and/or in the liver and to inhibition of the P-gp efflux transporter in the small intestine and/or reduction of total body clearance by nifedipine. The current study has raised awareness of potential drug interactions by concomitant use of repaglinide with nifedipine.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Reports - Volume 65, Issue 5, September–October 2013, Pages 1422–1430
نویسندگان
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