Pharmacokinetics of oral cyclosporin a (Sandimmun) in healthy subjects

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Abstract
Extensive pharmacokinetic (PK) profiles after oral dosing of 300 mg cyclosporin A (CsA) were determined in whole blood by radioimmunoassay (RIA) in 14 healthy male volunteers, using two-compartment models with either first order (M1) or zero order (M0) absorption. According to zero order absorption the mean of the following PK parameters was determined: terminal half-life=12.1±5.0 h, apparent volume of distribution at steady-state=5.6 ±2.1 l · kg−1, apparent clearance=0.51±0.11 l · h−1 · kg−1. The time lag between drug ingestion and first blood level was short, 0.38±0.11 h. Drug absorption lasted for 2.8±1.6 h. The end of absorption was indicated in each individual by a sharp drop in blood levels. The observations support the assumption that CsA is absorbed in the upper part of the small intestine with a clear-cut termination (absorption window). This assumption may explain the high degree of variability in the bioavailability of CsA.