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- W2078607056 abstract "The pharmacokinetics of cyclosporin A (CyA) were investigated in the rat following intravenous doses of 1·7, 3·3, and 6·4 mg kg−1 and oral doses of 3·1, 6·8, and 12·9 mg kg−1. The blood concentration-time profile after intravenous administration was adequately described by a two-compartment model when all data were simultaneously analysed using NONMEM. The disposition pharmacokinetics were linear over the dose range studied; the average total blood clearance was 0·191 g−1 kg−1. The absorption process could not be adequately described by either a first- or a zero-order input. Therefore, a flexible, staircase input model was used and found to be superior to the standard models. The shape of this model was biphasic, with a higher initial input rate than expected from first-order absorption. The duration of this first phase increased with dose. The extent of absorption was also dose dependent. Bioavailability was higher at higher doses; the values were 45%, 67% and 76% for the three ascending dose levels. These results strongly indicate a saturable first-pass effect. Since the extraction of CyA in the liver is only 6%, the marked increase in bioavailability of CyA is most likely to be the result of saturated gut wall metabolism." @default.
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- W2078607056 title "Dose dependent absorption and linear disposition of cyclosporin A in rat" @default.
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- W2078607056 doi "https://doi.org/10.1002/bdd.2510150107" @default.
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