Area Under the Curve Monitoring of Cyclosporine TherapyThe Early Posttransplant Period

摘要

Summary:The impact of a new monitoring strategy on whole blood concentrations of cyclosporine measured by a specific monoclonal radioimmunoassay was investigated in a group of 37 renal transplant patients. Before transplantation, the patients received a standard intravenous (i.v.) and oral (p.o.) test dose of cyclosporine to calculate their individual i.v. and p.o starting dose rates to achieve a certain target steady-state cyclosporine concentration. After transplantation, the designated i.v. dose rate was continuously infused for 2 days, at which time the steady-state concentration was measured. Then, the designated oral dose for 24 h was administered while the infusion was continued at an unaltered rate. The oral absorption of cyclosporine was documented by blood samples over the following 8 h. If necessary, this overlap of i.v. and p.o. dosing was repeated until blood concentrations of cyclosporine rose at least 700 ng/ml over the steady-state concentration. By that time, the infusion was stopped and oral dosing continued. Individualized infusions led to steady-state concentrations within a range that did not exceed 1.1 times the median concentration of 472 ng/ml. Standard infusion rates in the past produced a much wider range of steady-state concentrations (9.6 times the median). Individualized infusions reached the target steady-state concentration with a significant positive bias of 17percnt; (SEM = le;32percnt;, range of minus;36 to plus; 105percnt;). Individualized oral doses reached the target average steady-state concentration (calculated by dividing the area under the concentration-time curve by the dosing interval) with an inferior precision (median = 2.6percnt;, range of minus;54 to plus; 130percnt;) but without a positive or negative bias. Until 14 days after transplantation, 88percnt; of the patients showed satisfactory oral absorption of cyclosporine; the remaining 12percnt; were kept on infusions for up to 1 month. The new monitoring strategy rendered immunosuppression with cyclosporine and prednisone a safe and effective therapy after renal transplantation.