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 func tion 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. Patie nts entered (period I) and completed (period III) the investigation wi th the market formulation and received the microemulsion formulation i n period II; individualized cyclosporin doses remained unchanged throu ghout the study. Over one steady-state dosing interval at the end of e ach study period, whole blood cyclosporin pharmacokinetic profiles wer e assessed in parallel with endogenous creatinine clearances over sequ ential 1- to 2-h intervals. The rate and extent of cyclosporin absorpt ion were significantly greater (P < 0.01) from the microemulsion formu lation with average increases of 73 % in peak concentration and 44 % i n area under the curve compared to the market formulation. Sequential creatinine clearances exhibited a transient decrease with the nadir oc curring on average between 4 and 6 h post dose followed by a rapid ret urn to baseline. Specifically in period I on the market formulation, c learances decreased from a baseline of 71.7 +/- 20.6 to a minimum of 5 1.1 +/- 17.9 ml/min per 1.73 m(2) (similar values in period III) and f rom 76.8 +/- 24.8 to 53.5 +/- 17.5 ml/min per 1.73 m(2) in period II o n the microemulsion. Neither the baseline nor minimum clearances were significantly different among the study periods. Hence, the pharmacoki netic differences between the formulations did not acutely influence t he pattern of glomerular filtration rate following the initial milligr am-milligram to-milligram changeover in stable renal transplant patien ts.