Long-term cyclosporin A pharmacokinetic profiles in pediatric renal transplant recipients.
To study the long-term effect of cyclosporin A (CyA), 94 6-h and 29 12-h pharmacokinetic profiles were evaluated in 32 children at least 1 year after renal transplantation. Children weighing less than 25 kg needed significantly higher doses of CyA than those weighing more than 25 kg (9.8 vs 5.3 mg/kg per day; P < 0.001) to achieve similar trough levels (TL). The average dose of CyA required to achieve the target TL declined gradually with time after transplantation. The average area under the curve over 6 h (AUC/6) correlated strongly with the AUC/12 (r = 0.967; P < 0.001). The AUC/6 of patients with biopsy-proven CyA toxicity was significantly higher than for those without toxicity (Mann-Whitney U-test P < 0.05) despite similar TL. We conclude that AUC monitoring for 6 h provides valuable information not only on TL but also on the absorption and elimination characteristics of CyA as well as on the potential for CyA toxicity.
Department of Pediatric Nephrology, University Hospital Gasthuisberg, Leuven, Belgium.
A
A
Kelles
R
R
Van Damme-Lombaerts
T B
TB
Tjandra-Maga
B
B
Van Damme
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007223:Infant; D016030:Kidney Transplantation; D008297:Male; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine