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• W1968872289 abstract "The pharmacokinetics and bioavailability of intravenous, intraduodenal, buccal, rectal and percutaneous nifedipine were studied in rats to evaluate the influence of route of administration. Plasma concentrations of nifedipine were determined by electron capture gas-liquid chromatography with preliminary oxidation of the drug to its pyridine analog. Pharmacokinetic evaluations were carried out by noncompartmental analysis of plasma concentration-time curves based on the statistical moment theory. The moments were computed by fitting a polyexponential function to the discrete time-course data of plasma concentration using the iterative least-squares method. A good computer fit to biexponential kinetics and a short mean residence time were observed after intravenous administration (i. v.). The linear distribution and disposition of nifedipine was found within the dosing range tested (0.025-0.100 mg/kg, i. v.). The systemic availability of nifedipine after intraduodenal administration was on the average between 52% and 57%, indicating that nifedipine is extensively metabolized during first passage through the liver. Avoidance of first-pass metabolism was investigated following buccal, rectal and percutaneous administration to rats. These nonportal routes of administration gave approximately 10-30% increases in systemic availability compared to that from intraduodenal nifedipine delivery. Moment analysis revealed variations of mixing condition of nifedipine at the dosing site. It was shown that the absorption occurs in a mammillary manner after intraduodenal and rectal administration. On the other hand, there is steady-state absorption of the drug from the buccal route of administration. Following percutaneous administration, the drug seems to be absorbed catenary to some degree. The amount of intact drug absorbed-time curve following noninstantaneous administration was simulated by a deconvolution method. Percutaneous nifedipine, as well as buccal nifedipine, appears to be a promising administration route from the viewpoint of sustained and controlled drug absorption." @default.
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• W1968872289 date "1987-01-01" @default.
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• W1968872289 title "Moment analysis of intravenous, intraduodenal, buccal, rectal and percutaneous nifedipine in rats." @default.
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• W1968872289 doi "https://doi.org/10.1248/bpb1978.10.462" @default.
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