Substitution of conventional cyclosporin with a new microemulsion formulation in renal transplant patients: results after 1 year

BACKGROUND: A new galenic form of cyciosporin A has been developed, basedon microemulsion technology. The bioavailability of the compoundis reiativeiy independent of food intake and bile flow. It wasthe purpose of this prospective clinical trial to study thesafety of the microemulsion form of cyclosporin A. METHODS: Three hundred and two renal transplant patients, stratifiedaccording to transplant age, were switched from the conventionalto the new micro-emulsion formulation of cyclosporin A. A 1:1conversion ratio was used. Measurements included CsA levels,S-creatinine, liver enzymes, uric acid, and blood pressure.Measurements were performed at baseline and on days 4, 8, 15,29 and months 3, 6 and 12 after conversion. Dose adjustmentswere performed to achieve trough levels of 80–120 ng/ml. RESULTS: Within the 12-month observation period the cyclosporin dosewas reduced by 14.7% (from 204±60 mg/day at baselineto 174±51 mg/day after conversion, P<0.001). Acutely,i.e. by day 8, a 1:1 dose conversion resulted in a modest increaseof mean drug trough levels (from 114 ng/ml at baseline to 120ng/ml, P<0.01). This increase was accompanied by an increasein serum creatinine concentration, a decrease in calculatedcreatinine clearance, and an increase in uric acid values (P0.05).Liver enzymes remained unchanged while systolic and mean arterialblood pressure decreased (P<0.05). After 1 month, drug troughlevels had decreased to baseline (112 ng/ml) and remained thereuntil month 6. They were significantly lower after 12 months(102±33 ng/ml, P<0.001). Creatinine clearance valuesincreased to above baseline at 6 and 12 months. Within the 1-yearperiod there occurred 24 (=8%) episodes of biopsy-proven rejectionand seven episodes of cyclosporin-attributed nephrotoxicity. CONCLUSIONS: The 1:1 conversion from conventional cyclosporin A to the microemulsionformulation is efficacious and safe, but an initial dose reductionof 10% is advised in patients with trough levels in the high-normalrange.