Two-hour cyclosporine level determination is the appropriate tool to monitor Neoral therapy.

To assess the safety profile of Neoral dose adjustment using cyclosporine (CsA) trough levels (C0) compared with levels obtained 2 h after the morning dose (C2), 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 (C0: 100-200 ng/ml) or Group II (C2: 200-400 ng/ml). Abbreviated pharmacokinetics were obtained for the estimation of the AUC0-4 h. Renal function was assessed by serum creatinine and the cimetidine-modified creatinine clearance. C2 correlated better than C0 with the AUC0-4 h (r = 0.91 vs. 0.63). Initial Neoral dose (mg/kg/d) was similar in both groups (2.8 +/- 0.5 and 2.8 +/- 0.8), and was lower in Group II at the second visit (2.0 +/- 0.7 vs. 3.0 +/- 0.6, p = 0.0001). C2 levels decreased in Group II from 912 +/- 438 to 555 +/- 271 ng/ml (p = 0.01), without evidence of acute rejection on endomyocardial biopsies. After the second visit,-both groups were monitored with C2, 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 (138 +/- 59 vs. 168 +/- 37 mumol/L, p = 0.01) and was similar in both groups at the last visit. Neoral dose reduction based on C2 levels was not associated with acute rejection. The better correlation with the AUC0-4 h suggests that C2 may be more reliable than C0 for Neoral dose adjustment.

RCT Entities:   Population Interventions Outcomes