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

Am J Kidney Dis. 2004 Jun;43(6):1098-103. doi: 10.1053/j.ajkd.2004.03.021.

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 (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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anemia, Hypochromic / blood
  • Anemia, Hypochromic / drug therapy
  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / drug therapy
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Drug Interactions
  • Erythrocytes / chemistry
  • Female
  • Ferrous Compounds / administration & dosage
  • Ferrous Compounds / pharmacology*
  • Ferrous Compounds / therapeutic use
  • Humans
  • Intestinal Absorption / drug effects
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / blood
  • Mycophenolic Acid / metabolism
  • Mycophenolic Acid / pharmacokinetics*
  • Mycophenolic Acid / therapeutic use
  • Time
  • Time Factors

Substances

  • Ferrous Compounds
  • ferrous sulfate
  • Mycophenolic Acid