Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients

Abstract

Background: Oral administration of ferrous-sulfate was reported to decrease intestinal absorption of mycophenolate mofetil (MMF) in healthy Japanese individuals by 90%. Methods: We examined the effect of a single oral dose of ferrous sulfate on steady-state mycophenolic acid pharmacokinetics in 10 iron-deficient (hypochromic red blood cells >2.5%), Caucasian, long-term kidney graft recipients using a randomized, open-label, crossover design. On days A and B, MMF (1,000 mg) was given orally at 8:00 am. On day C, MMF and ferrous sulfate (105 mg) were coadministered at 8:00 am. On day D, MMF was given at 8:00 am and ferrous sulfate was given orally 4 hours later. Results: The interindividual variability of the 12-hour area under the plasma mycophenolic acid concentration versus time curves (AUC0–12) under control conditions was small (89.5 ± 27.8 and 87.6 ± 39.1 mg · h/L, respectively). Concomitant or subsequent administration of MMF and ferrous sulfate did not affect the bioavailabilty of MMF (AUC0–12, 91.9 ± 30.4 mg · h/L and 96.0 ± 31.7 mg · h/L). Conclusion: Oral therapy of iron deficiency using ferrous sulfate in long-term kidney graft recipients does not impede intestinal absorption of MMF; hence, exposure to this immunosuppressive agent is not reduced.