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 l 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.