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

Abstract

Background. A new galenic form of cyclosporin A has been developed, based on microemulsion technology. The bioavailability of the compound is relatively independent of food intake and bile flow. It was the purpose of this prospective clinical trial to study the safety of the microemulsion form of cyclosporin A. Methods, Three hundred and two renal transplant patients, stratified according to transplant age, were switched from the conventional to the new microemulsion formulation of cyclosporin A. A 1:1 conversion 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 adjustments were performed to achieve trough levels of 80-120 ng/ml. Results. Within the 12-month observation period the cyclosporin dose was reduced by 14.7% (from 204 ± 60 mg/day at baseline to 174 ± 51 mg/day after conversion, P<0.001). Acutely, i.e. by day 8: a 1:1 dose conversion resulted in a modest increase of mean drug trough levels (from 114ng/ml at baseline to 120 ng/ml, P<0.01). This increase was accompanied by an increase in serum creatinine concentration, a decrease in calculated creatinine clearance, and an increase in uric acid values (P≤0.05). Liver enzymes remained unchanged while systolic and mean arterial blood pressure decreased (P<0.05). After 1 month, drug trough levels had decreased to baseline (112 ng/ml) and remained there until month 6. They were significantly lower after 12 months 33ng/ml, P<0.001). Creatinine clearance increased to above baseline at 6 and 12 months. Within the 1-year period there occurred 24 (= 8%) episodes of biopsy-proven rejection and seven episodes of cyclesporin-attributed nephrotoxicity. Conclusions. The 1:1 conversion from conventional cyclosporin A to the microemulsion formulation is efficacious and safe, but an initial dose reduction of 10% is advised in patients with trough levels in the high-normal range.