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

In order to evaluate the pharmacokinetics of cyclosporine A comparing the t raditional (CsA-SCG) with the microemulsion formulation (CsA-ME), 20 clinic ally stable heart-transplant patients were enrolled in the study. All patie nts 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 concentrat ion-time curve during a dosage interval was calculated during three sequent ial 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 milligra m-to-milligram dose conversion). After switching from standard formulation CsA-SCG to CsA-ME, significant changes were observed in C-max(ss), (732 +/- 178 vs 935 +/- 250 ng ml(-1), P < 0.001) and t(max) (2.63 +/- 1.21 vs 1.36 +/- 0.49 h, P < 0.001), The CsA-ME mean bioavailability was higher than Cs A-SCG (75 +/- 19 vs 66 +/- 16%; P < 0.001). The main CsA pharmacokinetic pa rameters of both formulations in clinically stable heart-transplant patient s presented evident differences from data obtained in other transplant-pati ent populations. (C) 2001 Academic Press.