Two‐hour cyclosporine level determination is the appropriate tool to monitor Neoral therapy¹

Abstract

To assess the safety profile of Neoral dose adjustment using cyclosporine (CSA) trough levels (C 0 ) compared with levels obtained 2 h after the morning dose (C 2 ), 30 stable adult heart transplant patients 1 yr or more after surgery were converted from Sandimmune to Neoral. After a baseline visit (before conversion), initial follow‐up included two visits (2 and 4‐6 wk after conversion). After the first visit. patients were randomized to Group I (CC 2 : 100‐200 ng/ml) or Group II (CC 2 : 200‐400 ng/ml). Abbreviated pharmacokinetics were obtained for the estimation of the AUC 0‐4h 4 h. Renal function was assessed by serum creatinine and the cimetidine‐modified creatinine clearance. C 2 correlated better than C 0 with the AUC 0‐4h (r = 0.91 vs. 0.63). Initial Neoral dose (mg/kg/d) was similar in both groups (2.8±0.5 and 2.80.8), and was lower in Group II at the second visit (2.0±0.7 vs. 3.0±0.6, p = 0.0001). C 2 levels decreased in Group II from 912±438 to 555271 ng/ml (p=0.01), without evidence of acute rejection on endomyocardial biopsies. After the second visit, both groups were monitored with C 2 , and the range was increased to 300‐600 ng/ml. At the last visit (additional follow‐up of 5±1 months), Neoral dose (mg/ kg/d) was reduced to 2.0±0.3 in Group I (p<0.001) and 1.8 ±0.4 in Group II. Serum creatinine was lower in Group II at the second visit (13859 vs. 168±37 μmol/L, p = 0.01) and was similar in both groups at the last visit. Neoral dose reduction based on C 2 levels was not associated with acute rejection. The better correlation with the AUC 0‐4h suggests that C 2 may be more reliable than C 0 for Neoral dose adjustment.