PHARMACOKINETIC, HEMODYNAMIC, AND METABOLIC EFFECTS OF CYCLOSPORINE SANDIMMUNE VERSUS THE MICROEMULSION NEORAL IN HEART-TRANSPLANT RECIPIENTS

Background: Cyclosporine is a potent immunosuppressive agent that is, however, associated with systemic hypertension and renal dysfunction. The purpose of this investigation was to study the pharmacokinetic and long-term renal and hypertensive effects of Sandimmune (Sandoz) versu s the new Neoral (Novartis) formulation of cyclosporine in heart trans plant recipients. Methods: Twenty heart transplant recipients with sta ble conditions and aged 54 +/- 9 years were studied in an open-labeled single-arm conversion protocol. Twelve-hour pharmacokinetic studies w ere performed on Sandimmune and after 4 weeks of treatment with Neoral at similar dosage. The 24-hour blood pressure monitoring, creatinine clearance, and complete biochemistry profile were studied simultaneous ly to the pharmacokinetic studies. Six-month follow-up with serial mea surements of cyclosporine levels, and biochemistry profile was complet ed. Results: Conversion to Neoral resulted in a 24% increase in area-u nder-the-curve in spite of no significant changes in cyclosporine trou gh levels (165 +/- 48 [Sandimmune] vs 169 +/- 32 nmol/L; p = 0.26). Re spectively, 16%, 68%, and 16% were poor, average, and good absorbers o n Sandimmune versus 26% and 74% being average or good absorbers on Neo ral. Averaged systolic and diastolic blood pressure were not affected by Neoral, but blood pressure readings increased in 20% of patients pr eviously known as having hypertension. The 24-hour blood pressure data yielded no significant changes with Neoral, but the nocturnal drop in systolic blood pressure was attenuated by Neoral. Twenty-four-hour cr eatinine clearance was not affected by Neoral, but serum magnesium lev els decreased significantly at 6 months. Conclusions: Neoral resulted in 24% increase in cyclosporine exposure without significant changes i n trough levels, and improved absorption status. This greater drug exp osure is well tolerated and resulted in a slight increase in blood pre ssure in a subset of patients and some decrease in magnesium levels, b ut it had no effect on renal function.