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

Cyclosporine is usually prescribed as ''mg CsA per kg body weight'', a nd blood levels are used for guiding CsA therapy. The present study ev aluated whether it is sensible to dose in ''mg/kg'' if one wishes to o btain specific CsA blood levels. In a retrospective analysis, 1071 con secutive CsA whole-blood trough levels from 164 renal transplant patie nts, measured by monoclonal parent RIA, were correlated with the respe ctive oral CsA doses and several demographic parameters, including gen der, age, weight, height, and time after transplantation. From this, w e derived a concept of ''weight-independent CsA dosing'' which was pro spectively tested in three series of patients during the first days af ter renal transplantation: 58 patients received 2 x 100 mg/day CsA fro m day 0 with the intention to reach target levels of 40-80 ng/ml, 42 p atients 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-specifi c relation of CsA level to CsA dose (in mg) was found to depend only o n 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'', pat ients less than or equal to 55 kg b. wt. required nearly twice the dos es 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 prospec tive studies, median CsA levels after three days of CsA therapy were 5 7 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 conc lusion, there is no rationale for dosing CsA in ''mg/kg'', if one aims at specific CsA trough levels. Irrespective of weight, median CsA lev els (in ng/ml) approximate 0.3 times the daily oral CsA dose (in mg) i n the first days after transplantation, and this relation gradually in creases for several years. The initial CsA dose after renal transplant ation should be independent of weight, particularly in settings where level determinations are unavailable.