Absorption of cyclosporin from conventional and new microemulsion oral formulations in liver transplant recipients with external biliary diversion.

Abstract

1. Less than 5% of a dose of the conventional oral formulation of cyclosporin, Sandimmun, is absorbed in liver transplant recipients with external biliary drainage, necessitating intravenous administration of the drug and exposing the patient to increased risk of severe side-effects. 2. We compared the pharmacokinetics of the conventional oral formulation of cyclosporin with that of the new microemulsion formulation, Neoral, in eight liver transplant recipients with external biliary diversion. Patients were maintained on a continuous infusion of cyclosporin until steady-state conditions had been achieved. They were then given a test dose (10 mg kg-1) of either the conventional or microemulsion formulation (randomised order) followed by the same dose of the other formulation. Parent cyclosporin concentrations were measured in whole blood samples collected at timed intervals over the 24 h after the oral doses and pharmacokinetic parameters calculated. 3. The bioavailability of cyclosporin from the microemulsion formulation was, on average, 6.5-fold (95% C.I. 1.9 to 11.1-fold) greater than that of the conventional formulation, indicating the improved absorption characteristics of the new oral microemulsion formulation during external bile drainage. 4. A significant negative correlation was found between the external bile drainage volume and bioavailability of cyclosporin from the microemulsion formulation (r = -0.8; P = 0.016), suggesting that variability in cyclosporin absorption from the microemulsion formulation may still be at least partly attributable to bile- dependence.(ABSTRACT TRUNCATED AT 250 WORDS)