Reduced intrapatient variability of cyclosporine pharmacokinetics in renaltransplant recipients switched from oral Sandimmune to Neoral

Sixty-six renal transplant patients maintained on Sandimmune(R), the tradit ional formulation of cyclosporine, participated in an open-label, sequentia l trial to compare intrapatient variability in drug exposure before and aft er a switch to Neoral(R). Three 12-hour cyclosporine pharmacokinetic profil es were obtained over approximately 6 weeks while patients were receiving S andimmune. patients were then switched to Neoral, with the dose adjusted as necessary to maintain target trough blood cyclosporine concentrations. At approximately 4 and 6 weeks postconversion, 2 additional pharmacokinetic pr ofiles were obtained. Key pharmacokinetic variables analyzed were area unde r the concentration-time curve (AUC), maxi- mum concentration (C-max), and predose trough concentration (C-0) Intrapatient variability in drug exposur e for dose-normalized mean AUG, C-max and C-0 was significantly reduced wit h Neoral, with 50 (76%), 57 (86%), and 45 (68%) patients experiencing reduc ed variability in AUG, C-max, and C-0, respectively (P < 0.001). Additional ly, the total exposure to cyclosporine was more predictable from the trough level of cyclosporine with Neoral; the relationship between AUC and C-0 wa s 0.81 for Neoral at both pharmacokinetic profiling time points but ranged from 0.49 to 0.69 for the 3 Sandimmune time points. The large reductions in intrapatient variability of pharmacokinetic variables for cyclosporine pro vided by Neoral indicate an improvement in the consistency of drug exposure , which may translate into important clinical benefits.