Effect of food components and dosing times on the oral pharmacokinetics of nifedipine in rats


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Abstract

The present study was aimed to investigate the effect of food components and dosing time on the oral exposure of nifedipine in rats. Nifedipine was given orally to rats with and without food components at 8:00 a.m. (morning time) or 4:00 p.m. (evening time) during winter periods. Food components included milk, sodium chloride, oleic acid, and sodium taurocholate. Plasma concentration profiles of nifedipine showed double peak phenomena which were generally retained regardless of food components, vehicle types and the dosing time. Sodium chloride, milk and sodium taurocholate significantly increased the AUC while oleic acid did not, when drug was dosed in the morning time. After the dosing in the evening time, milk and sodium chloride significantly increased the plasma concentrations of nifedipine but oleic acid and sodium taurocholate decreased them. Overall, the systemic in vivo exposure of nifedipine was invariably lower with the evening dosing compared to the dosing in the morning, but this circadian rhythm dependency was not reversed by the multiple dosing of food components in rats. Food components and dosing time significantly altered the oral pharmacokinetics of nifedipine in rats, implying that the altered bioavailability and higher plasma concentrations in the morning time may influence dosing regimens of nifedipine for hypertension patients.

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