Background/aims: The present study evaluated the clinical efficacy and pharmacokinetics of microemulsion cyclosporine A (ME-CyA) with modification from postprandial to preprandial administration in adult patients with refractory nephrotic syndrome.
Methods: We investigated 19 patients with refractory nephrotic syndrome who had been switched from the postprandial administration of ME-CyA to preprandial administration. The pharmacokinetics of ME-CyA were also evaluated before and 6 months after switching from postprandial to preprandial administration by serial measurement of the blood CyA concentration in 10 patients.
Results: This study showed that 16 of 19 patients (84%) displayed an improvement in their clinical condition or continued to maintain remission after switching from post- to preprandial administration. In particular among 14 patients with minimal change nephrotic syndrome (MCNS) in this study, 13 patients maintained or achieved remission under preprandial ME-CyA administration. Only three of 10 patients with postprandial administration showed a peak concentration> 500 ng/ml within 1-2 h after administration, while with preprandial administration, nine of 10 patients showed this good absorption profiles. This effectiveness of preprandial administration seems to be dependent on the improved pharmacokinetics with the increase of area under the curve from 0-4 h (AUC(0-4)) and peak concentration. There were no statistical differences in the mean daily doses of ME-CyA between both administration periods. No ME-CyA-induced nephrotoxicity or other harmful events were encountered throughout the study.
Conclusion: The preprandial administration of ME-CyA results in a good pharmacokinetic profile and is useful for management of refractory nephrotic syndrome in adults, particularly in patients with MCNS.