Mycophenolic Acid Formulation Affects Cyclosporine Pharmacokinetics in Stable Kidney Transplant Recipients

A novel monitoring strategy based on the blood concentration at two hours post-dose (C2) has been recently proposed for the assessment of cyclosporine (CsA) absorption and daily exposure, and therapeutic windows for C2 levels have been identified. These guidelines have been derived from patients given mycophenolate mofetil (MMF) or azathioprine, and never tested in those treated with the enteric-coated formulation of mycophenolic acid (EC-MPS). The authors have compared full CsA pharmacokinetic evaluations in 12 kidney transplant recipients given EC-MPS with those from 20 patients on MMF at months 6, 12, 18 and 24 postsurgery. At month 6 postsurgery, patients on EC-MPS had a shift to the right in the CsA peak concentration as compared to that in patients given MMF, an effect associated with significant differences in CsA Tmax (1.9 +/- 0.3 h vs. 1.5 +/- 0.6 h, P < 0.05), C2 (988 +/- 259 vs. 720 +/- 214 ng/mL, P < 0.01), and C3 levels (539 +/- 119 vs. 435 +/- 119 ng/mL, P < 0.05). Interestingly, the authors found that the majority of patients on EC-MPS had CsA peaking at 2-h postdosing, whereas most of patients on MMF had CsA Cmax at 1 h. Similar results were observed also at months 12, 18, and 24 postsurgery. These findings indicate that the pharmacokinetics of CsA is significantly affected by the concomitant administration of different MPA formulations. This would imply the need of specific algorithms to adequately estimate CsA dose adjustment in patients given, in addition to CsA, EC-MPS or MMF.