Pretransplant test-dose pharmacokinetic profiles

The purpose of this study was to compare the accuracy of pretransplant test-dose pharmacokinetic (PK) profiling after administration of the microemulsion (CsA-ME; Neoral) versus the corn oil-based (CsA-GC; Sandimmune) gel capsule formulations of cyclosporin A (CsA) to estimate posttransplant CsA bioavailability and to individualize starting drug doses. The absolute oral bioavailability (F), clearance rate (CL), average blood concentration (C[av]), peak concentration (Cmax), and time to Cmax (tmax) values were calculated from paired intravenous and oral pretransplant PK profiles of renal transplant candidates, using CsA-GC (n = 70) or CsA-ME (n = 70) administration. The initial posttransplant oral CsA dose was estimated by linear extrapolation of the observed pretransplant value to the target concentration. Because higher mean F (P 700 ng/ml in 90% of patients from days 2 to 4, and in 97% from days 5 to 7, whereas administration of the predicted oral dose of CsA-GC produced a Cmax > 700 ng/ml in only 64 and 82% of patients during these same time periods, respectively (both P < 0.05). The mean estimated posttransplant F value of CsA-ME was significantly higher than that of CsA-GC; even at postoperative day 5 the value for CsA-GC was significantly lower than the pretransplant estimate (P < 0.01). Therefore, CsA-ME pretransplant PK profiles yield more accurate predictions for appropriate starting drug doses than those of CsA-GC.