UNLABELLED: This study sought to evaluate the bioequivalence of Iminoral (test) versus Neoral (reference) in healthy volunteers, as well as safety and efficacy of Iminoral treatment in renal transplant recipients following conversion from Neoral. METHODS: After an overnight fast, 18 healthy volunteers received the assigned treatment (test or reference, 200 mg single dose) in a cross-over fashion with a washout period of 14 days. The blood samples were drawn at various times after drug administration. Cyclosporine blood concentration was measured by high-performance liquid chromatography using an ultraviolet detector. In the second phase of study, stable renal transplant patients who were on Neoral were enrolled in the study in an open-label manner. They were converted from Neoral to Iminoral based on a 1:1 dose equivalence. Cyclosporine trough levels and changes in serum creatinine, lipid profile, electrolytes, and uric acid were measured before and periodically after conversion for 6 months. RESULTS: The 90% confidence interval of the test/reference ratio was within the acceptable limits of 0.8 to 1.25. Relative bioavailability of Iminoral in healthy subjects was 99.0%. There was no significant difference in cyclosporine concentrations and serum creatinines following conversion to Iminoral in renal transplant patients (n=41). There were no reports of major toxicity or of graft rejection and no need for dose adjustment related to Iminoral. CONCLUSIONS: Single doses of Neoral and Iminoral are bioequivalent in healthy subjects. Renal transplant recipients maintained on Neoral can be safely and effectively converted to Iminoral on a 1:1 conversion ratio.
RCT Entities:
UNLABELLED: This study sought to evaluate the bioequivalence of Iminoral (test) versus Neoral (reference) in healthy volunteers, as well as safety and efficacy of Iminoral treatment in renal transplant recipients following conversion from Neoral. METHODS: After an overnight fast, 18 healthy volunteers received the assigned treatment (test or reference, 200 mg single dose) in a cross-over fashion with a washout period of 14 days. The blood samples were drawn at various times after drug administration. Cyclosporine blood concentration was measured by high-performance liquid chromatography using an ultraviolet detector. In the second phase of study, stable renal transplant patients who were on Neoral were enrolled in the study in an open-label manner. They were converted from Neoral to Iminoral based on a 1:1 dose equivalence. Cyclosporine trough levels and changes in serum creatinine, lipid profile, electrolytes, and uric acid were measured before and periodically after conversion for 6 months. RESULTS: The 90% confidence interval of the test/reference ratio was within the acceptable limits of 0.8 to 1.25. Relative bioavailability of Iminoral in healthy subjects was 99.0%. There was no significant difference in cyclosporine concentrations and serum creatinines following conversion to Iminoral in renal transplant patients (n=41). There were no reports of major toxicity or of graft rejection and no need for dose adjustment related to Iminoral. CONCLUSIONS: Single doses of Neoral and Iminoral are bioequivalent in healthy subjects. Renal transplant recipients maintained on Neoral can be safely and effectively converted to Iminoral on a 1:1 conversion ratio.
Authors: Amber O Molnar; Dean Fergusson; Anne K Tsampalieros; Alexandria Bennett; Nicholas Fergusson; Timothy Ramsay; Greg A Knoll Journal: BMJ Date: 2015-06-22