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 (AUC(0-12)) under control conditions was small (89.5 +/- 27.8 and 87.6 +/- 39.1 mg x h/L, respectively). Concomitant or subsequent administration of MMF and ferrous sulfate did not affect the bioavailabilty of MMF (AUC(0-12), 91.9 +/- 30.4 mg x h/L and 96.0 +/- 31.7 mg x 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.
RCT Entities:
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 (AUC(0-12)) under control conditions was small (89.5 +/- 27.8 and 87.6 +/- 39.1 mg x h/L, respectively). Concomitant or subsequent administration of MMF and ferrous sulfate did not affect the bioavailabilty of MMF (AUC(0-12), 91.9 +/- 30.4 mg x h/L and 96.0 +/- 31.7 mg x 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.
Authors: Gere Sunder-Plassmann; Petra Reinke; Thomas Rath; Andrzej Wiecek; Michal Nowicki; Richard Moore; Jens Lutz; Martina Gaggl; Marek Ferkl Journal: Transpl Int Date: 2012-04-16 Impact factor: 3.782