Decreased oral availability of cyclosporin A at second administration in humans.
OBJECTIVE
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.
Lee
Y J
YJ
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Korea.
Chung
S J
SJ
Shim
C K
CK
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D013810:Therapeutic Equivalency
D007166:Immunosuppressive Agents; D016572:Cyclosporine