Acute effect of cyclosporin 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 sequential 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 m2 (similar values in period III) and from 76.8 +/- 24.8 to 53.5 +/- 17.5 ml/min 1.73 m2 in period II on the microemulsion. Neither the baseline nor minimum clearances were significantly different among the study periods.(ABSTRACT TRUNCATED AT 250 WORDS)
Kovarik
J M
JM
Department of Clinical Pharmacology, Sandoz Pharma Ltd., Basel, Switzerland.
Kallay
Z
Z
Mueller
E A
EA
van Bree
J B
JB
Arns
W
W
Renner
E
E
D000328:Adult; D003404:Creatinine / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004655:Emulsions; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects*; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine