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Decreased oral availability of cyclosporin A at second administration in humans
1Department of Pharmaceutics, College of Pharmacy, Seoul National University, Korea.
Aims:
The objective of this study was to determine the extent of period effect on the pharmacokinetics of cyclosporin A (CsA) during consecutive dosing.
Methods:
Sandimmune Neoral and Neoplanta capsules were administered to twenty-four healthy Korean male subjects at a single CsA dose of 175 mg in a 2 x 2 crossover investigation with a 2-week wash-out phase. Concentrations of CsA in blood were measured by a r.i.a. method for a period of 48 h.
Results:
The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant (P < 0.01) period effect in AUC(0,last) (area under the blood concentration-time curve above the assay limit) and Cmax (maximum blood concentration) between the administrations. A 6 and 9% decrease in the AUC(0,last) and Cmax, respectively was seen at the second administration.
Conclusions:
This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug.
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