Abstract
1. The pharmacokinetics of cyclosporine (CsA) and the time course of CsA metabolites were studied in five bone marrow transplant patients after intravenous (i.v.) administration on two separate occasions and once after oral CsA administration. 2. Cyclosporine and cyclosporine metabolites were measured in whole blood by h.p.l.c. 3. Cyclosporine clearance after i.v. administration decreased from 3.9 +/- 1.7 ml min-1 kg-1 to 2.0 +/- 0.6 ml min-1 kg-1 after 14 days of treatment. The mean +/- s.d. absolute oral bioavailability of cyclosporine was 17 +/- 11%. 4. Hydroxylated CsA (M-17) was the major metabolite in blood. There were no significant differences in the mean metabolite/CsA AUC ratios between the first and second i.v. studies. 5. After oral administration, the metabolite to CsA AUC ratios were higher for most metabolites compared to those observed in the second i.v. study, suggesting a contribution of intestinal metabolism to the clearance of CsA.
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