Standard dose enteric-coated mycophenolate sodium (myfortic) delivers rapid therapeutic mycophenolic acid exposure in kidney transplant recipients

Abstract

Previous studies have shown poor absorption of enteric-coated mycophenolate sodium (E-MPS) during the initial post-kidney transplantation (KT) period. The percentage of patients with adequate therapeutic exposure (target AUC 30-60 μg.h/mL) of mycophenolic acid is 55%, 86%, and 100% at days 14, 90, and 180 postgrafting. To assess the adequacy of mycophenolic acid (MPA) delivery during the initial period, we prospectively studied the pharmacokinetics (AUC0-12h) of MPA (measured by high-performance liquid chromatography) in 12 patients after their first single dose of 720 mg of oral E-MPS and 3 to 8 months after 720 mg twice a day prescribed daily. Concomitant immunosuppression included CsA and prednisolone. Evaluation of the pharmacokinetic profiles was repeated at 2 weeks. The patients' mean ± SD body weight was 48.1 ± 8.8 kg; their mean (range) values of AUC0-12hfor MPA were 73.9 ± 49.5 μg.h/ml (31.9-190) on day 1 and 74.3 ± 44.3 (30.5-178) μg.h/ml on day 14. The mean nadir serum creatinine was 1.1 ± 0.4 mg/dL. The patient and graft survival rates were 100%. Two patients (15%) developed significant diarrhea requiring E-MPS dose reduction. Other complications included urinary tract infections (n = 2), CMV syndrome (n = 1), borderline acute rejection (n = 1), and reversible CsA nephrotoxicity (n = 3). We conclude that the use of a standard dose of E-MPS results in immediate delivery of adequate therapeutic systemic MPA exposure in all patients. The absorption profile was better than that described previously. © 2005 by Elsevier Inc. All rights reserved.