Pharmacokinetics of cyclosporine in toxicological studies.

Pharmacokinetic studies performed in toxicological studies indicate that CsA is well absorbed in rats and dogs with absolute bioavailability in the range of 10% to 30% when administered by gavage (olive oil). Exceptions are the guinea pig, the rabbit and marmoset with low bioavailability (less than 5%). CsA is also absorbed in rats when given mixed in the feed. Vehicles may have marked effects on the absolute bioavailability. The correlation between areas under the plasma concentration time curves (AUC) and dose levels is linear in most species up to a dose of 50 mg/kg/d. CsA steady state plasma levels are generally 2 to 3 times higher than after single administration. Measures to reduce CsA nephrotoxicity must consider possible changes of oral bioavailability and immunosuppressive activity as shown for dmPGE2. Drug interactions may be predicted in animal experiments.