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) versus the new Neoral (Novartis) formulation of cyclosporine in heart transplant recipients. METHODS: Twenty heart transplant recipients with stable conditions and aged 54 +/- 9 years were studied in an open-labeled single-arm conversion protocol. Twelve-hour pharmacokinetic studies were 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 simultaneously to the pharmacokinetic studies. Six-month follow-up with serial measurements of cyclosporine levels, and biochemistry profile was completed. RESULTS: Conversion to Neoral resulted in a 24% increase in area-under-the-curve in spite of no significant changes in cyclosporine trough levels (165 +/- 48 [Sandimmune] vs 169 +/- 32 nmol/L; p = 0.26). Respectively, 16%, 68%, and 16% were poor, average, and good absorbers on Sandimmune versus 26% and 74% being average or good absorbers on Neoral. Averaged systolic and diastolic blood pressure were not affected by Neoral, but blood pressure readings increased in 20% of patients previously 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 creatinine clearance was not affected by Neoral, but serum magnesium levels decreased significantly at 6 months. CONCLUSIONS: Neoral resulted in 24% increase in cyclosporine exposure without significant changes in trough levels, and improved absorption status. This greater drug exposure is well tolerated and resulted in a slight increase in blood pressure in a subset of patients and some decrease in magnesium levels, but it had no effect on renal function.
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) versus the new Neoral (Novartis) formulation of cyclosporine in heart transplant recipients. METHODS: Twenty heart transplant recipients with stable conditions and aged 54 +/- 9 years were studied in an open-labeled single-arm conversion protocol. Twelve-hour pharmacokinetic studies were 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 simultaneously to the pharmacokinetic studies. Six-month follow-up with serial measurements of cyclosporine levels, and biochemistry profile was completed. RESULTS: Conversion to Neoral resulted in a 24% increase in area-under-the-curve in spite of no significant changes in cyclosporine trough levels (165 +/- 48 [Sandimmune] vs 169 +/- 32 nmol/L; p = 0.26). Respectively, 16%, 68%, and 16% were poor, average, and good absorbers on Sandimmune versus 26% and 74% being average or good absorbers on Neoral. Averaged systolic and diastolic blood pressure were not affected by Neoral, but blood pressure readings increased in 20% of patients previously 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 creatinine clearance was not affected by Neoral, but serum magnesium levels decreased significantly at 6 months. CONCLUSIONS: Neoral resulted in 24% increase in cyclosporine exposure without significant changes in trough levels, and improved absorption status. This greater drug exposure is well tolerated and resulted in a slight increase in blood pressure in a subset of patients and some decrease in magnesium levels, but it had no effect on renal function.