Pharmacokinetics of two oral cyclosporin a formulations in clinically stable heart-transplant patients

In order to evaluate the pharmacokinetics of cyclosporine A comparing the traditional (CsA-SCG) with the microemulsion formulation (CsA-ME), 20 clinically stable heart-transplant patients were enrolled in the study. All patients were on a thrice-daily dosage regimen (mean single dose 1.14±0.4 mg kg-1 body weight) of CsA-SCG. The steady-state area under the concentration-time curve during a dosage interval was calculated during three sequential periods: (1) the first after the morning oral dose of CsA-SCG; (2) the second (8 days later) after 2 hours intravenous infusion of cyclosporine; (3) the third after the CsA-ME morning oral dose (30 days after the milligram-to-milligram dose conversion). After switching from standard formulation CsA-SCG to CsA-ME, significant changes were observed in Cmax/ss (732 ± 178 vs 935 ± 250 ng ml-1, P < 0.001) and tmax (2.63 ± 1.21 vs 1.36 ± 0.49 h, P < 0.001). The CsA-ME mean bioavailability was higher than CsA-SCG (75 ± 19 vs 66 ± 16%; P < 0.001). The main CsA pharmacokinetic parameters of both formulations in clinically stable heart-transplant patients presented evident differences from data obtained in other transplant-patient populations. © 2001 Academic Press.