Pharmacokinetics of cyclosporin in children with stable renal transplants

Fourteen children, aged between 5 and 17 years, with stable renal graft fun ction and stable cyclosporin A (CSA) trough levels (Cmin) were studied. The y had been taking CSA 12-hourly since their transplant 1.5-9 years previous ly, with the average dose of Neoral being 6.4 (range 4.4-8.4) mg/kg per day . CSA whole blood levels were measured at 0, 20, and 40 min, and at 1, 1.5, 2, 2.5, 3, 4, 6, and 8 h following the morning dose using the Abbott TDx f luorescence polarization immunoassay. The area under the concentration time curve (AUC), clearance adjusted for bioavailability (CL/F), and steady-sta te volume of distribution adjusted for bioavailability (Vss/F) were determi ned using model-independent pharmacokinetic analysis. Delay time (Tdel), pe ak concentration (Cmax), time to peak concentration (Tmax), and Cmin were a lso determined and correlated with AUC and other parameters. The Tdel in ab sorption varied from 0.3 to 1.6 (mean 0.73) h, resulting in a similarly var iable time to Tmax of 1-2.4 h (mean 1.59). Tmax was related to the age of t he patient (Tmax=0.027aget1.41, r(2)=0.56, P<0.005). The AUC showed good co rrelation with Cmax (Cmax=0.25AUC+423.32, r(2)=0.96, P<0.0005). Cmax appear s to be a more-suitable measure of exposure to CSA than Cmin. Prediction of Tmax from the age of the child may help to overcome the problem of when to collect blood for peak levels.