WEIGHT-INDEPENDENT DOSING OF CYCLOSPORINE - AN ALTERNATIVE TO THE MG/KG DOCTRINE

Cyclosporine is usually prescribed as ''mg CsA per kg body weight'', and blood levels are used for guiding CsA therapy. The present study evaluated whether it is sensible to dose in ''mg/kg'' if one wishes to obtain specific CsA blood levels. In a retrospective analysis, 1071 consecutive CsA whole-blood trough levels from 164 renal transplant patients, measured by monoclonal parent RIA, were correlated with the respective oral CsA doses and several demographic parameters, including gender, age, weight, height, and time after transplantation. From this, we derived a concept of ''weight-independent CsA dosing'' which was prospectively tested in three series of patients during the first days after renal transplantation: 58 patients received 2 x 100 mg/day CsA from day 0 with the intention to reach target levels of 40-80 ng/ml, 42 patients received 2 x 200 mg/day CsA from day 4 (target: 100-200 ng/ml), and 38 patients received 2 x 300 mg/day from day 4 (target: 100-200 ng/ml). In the retrospective analysis, the individual, patient-specific relation of CsA level to CsA dose (in mg) was found to depend only on height (P=0.02) and time after transplantation (P<0.001), but not on body weight (b. wt.). If the CsA dose was expressed in ''mg/kg'', patients less than or equal to 55 kg b. wt. required nearly twice the doses of patients greater than or equal to 75 kg b. wt., whereas the mean CsA requirement was the same when expressed in ''mg''. In the prospective studies, median CsA levels after three days of CsA therapy were 57 ng/ml on 2 x 100 mg/day, 129 ng/ml on 2 x 200 mg/day, and 160 ng/ml on 2 x 300 mg/day. Approximately half the patients in each group were in the target range, and levels did not correlate with weight. In conclusion, there is no rationale for dosing CsA in ''mg/kg'', if one aims at specific CsA trough levels. Irrespective of weight, median CsA levels (in ng/ml) approximate 0.3 times the daily oral CsA dose (in mg) in the first days after transplantation, and this relation gradually increases for several years. The initial CsA dose after renal transplantation should be independent of weight, particularly in settings where level determinations are unavailable.