Pharmacokinetics of cyclosporin in children with stable renal transplants.
Fourteen children, aged between 5 and 17 years, with stable renal graft function and stable cyclosporin A (CSA) trough levels (Cmin) were studied. They had been taking CSA 12-hourly since their transplant 1.5-9 years previously, 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 fluorescence polarization immunoassay. The area under the concentration time curve (AUC), clearance adjusted for bioavailability (CL/F), and steady-state volume of distribution adjusted for bioavailability (Vss/F) were determined using model-independent pharmacokinetic analysis. Delay time (Tdel), peak concentration (Cmax), time to peak concentration (Tmax), and Cmin were also determined and correlated with AUC and other parameters. The Tdel in absorption varied from 0.3 to 1.6 (mean 0.73) h, resulting in a similarly variable time to Tmax of 1-2.4 h (mean 1.59). Tmax was related to the age of the patient (Tmax = 0.027 age + 1.41, r2 = 0.56, P < 0.005). The AUC showed good correlation with Cmax (Cmax = 0.25 AUC + 423.32, r2 = 0.96, P < 0.0005). Cmax appears 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.
Tam
J C
JC
Centre for Kidney Research, Royal Alexandra Hospital for Children, PO Box 3515, Parramatta, NSW Australia 2124.
Earl
J W
JW
Willis
N S
NS
Farquhar
J E
JE
Nath
C E
CE
Knight
J F
JF
Hodson
E M
EM
D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male
D007166:Immunosuppressive Agents; D016572:Cyclosporine