Improved cyclosporine pharmacokinetics in maintenance renal transplant recipients converted to cyclosporine for microemulsion.
BACKGROUND
Variability in cyclosporine drug exposure of > or = 20% has been shown to be a risk factor for the development of chronic renal allograft rejection. We tested the hypothesis that a cyclosporine microemulsion (CsA-ME) would result in reduced variability in stable maintenance renal transplant patients when compared with the original formulation of cyclosporine (CsA).


METHODS
The 31 maintenance renal transplant recipients were part of a multicenter, randomized, double-blind, prospective study comparing the CsA formulation with the CsA-ME formulation. Pharmacokinetics analyses were performed at two centers 1, 4, 12, and 52 weeks after patients were randomized to continue receiving CsA or to convert to CsA-ME.


RESULTS
The means of the week 1-, 4-, and 12-week areas under the concentration-time curves (AUC), and Cmax were significantly higher and the Tmax was significantly shorter in those patients converted to CsA-ME than in those remaining on CsA. There was no correlation between change in AUC after conversion and change in serum creatinine. The coefficient of variation values for dose-adjusted AUC, expressed as a percentage (%CVAUC), were lower in CsA-ME patients than CsA patients after both 12 and 52 weeks. Over the initial 12 weeks. %CVAUC values of < or = 20% were seen in a significantly greater proportion of CsA-ME patients than CsA patients.


CONCLUSIONS
Conversion of maintenance renal transplant recipients from CsA to CsA-ME resulted in improved absorption of cyclosporine. The CsA-ME formulation resulted in long-term reduction in the variability of cyclosporine exposure and more consistent pharmacokinetics.
Department of Surgery, Indiana University, Indianapolis, IN 46202-5250, USA. mpescov@indyvax.iupui.edu
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D000328:Adult; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine