ACUTE EFFECT OF CYCLOSPORINE ON RENAL-FUNCTION FOLLOWING THE INITIAL CHANGEOVER TO A MICROEMULSION FORMULATION IN STABLE KIDNEY-TRANSPLANT PATIENTS

Potential differences in the acute effect of cyclosporin on renal function when dosed orally as the current market formulation or following a milligram-to-milligram conversion to a new microemulsion formulation were investigated in 14 stable kidney transplant patients. The study consisted of three se quential periods of 2 weeks duration each. Patients entered (period I) and completed (period III) the investigation with the market formulation and received the microemulsion formulation in period II; individualized cyclosporin doses remained unchanged throughout the study. Over one steady-state dosing interval at the end of each study period, whole blood cyclosporin pharmacokinetic profiles were assessed in parallel with endogenous creatinine clearances over sequential 1- to 2-h intervals. The rate and extent of cyclosporin absorption were significantly greater (P < 0.01) from the microemulsion formulation with average increases of 73 % in peak concentration and 44 % in area under the curve compared to the market formulation. Sequential creatinine clearances exhibited a transient decrease with the nadir occurring on average between 4 and 6 h post dose followed by a rapid return to baseline. Specifically in period I on the market formulation, clearances decreased from a baseline of 71.7 +/- 20.6 to a minimum of 51.1 +/- 17.9 ml/min per 1.73 m(2) (similar values in period III) and from 76.8 +/- 24.8 to 53.5 +/- 17.5 ml/min per 1.73 m(2) in period II on the microemulsion. Neither the baseline nor minimum clearances were significantly different among the study periods. Hence, the pharmacokinetic differences between the formulations did not acutely influence the pattern of glomerular filtration rate following the initial milligram-milligram to-milligram changeover in stable renal transplant patients.