Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients.
OBJECTIVE
To determine if coadministration of polysaccharide iron complex and slow-release ferrous sulfate alter the absorption of mycophenolic acid (MPA), and to examine the potential influence of dosing relative to mycophenolate mofetil (MMF) administration and the effect of immediate- versus sustained-release iron products on the steady-state pharmacokinetics of MPA.


METHODS
Prospective, open-label, three-phase, crossover, steady-state pharmacokinetic study.


METHODS
National Institutes of Health-sponsored General Clinical Research Center at a university medical center.


METHODS
Twelve adult (mean age 50 yrs) renal transplant recipients who were receiving concomitant iron and MMF maintenance therapy.


METHODS
Oral iron therapy was coadministered with MMF on days -6-0, MMF was administered alone on days 1-8 (control phase), then oral iron therapy was administered 2 hours after MMF administration on days 9-16.


RESULTS
Baseline demographics, concurrent drug regimens, and clinical laboratory values were assessed. Blood samples were obtained at baseline and at 1, 2, 3, 4, 6, 8, and 12 hours after MMF administration on days 0, 8, and 16. The MPA levels were measured by high-performance liquid chromatography. We found no significant differences in the dose-standardized area under the concentration-time curve from 0-12 hours (AUC(0-12)) for MPA between the control phase (39.66 +/- 8.70 mg mg x hr/L) and the concomitant ferrous sulfate or dose-separated ferrous sulfate (37.56 +/- 9.95 or 32.84 +/- 8.43 mg x hr/L, respectively, p>0.05) phases. Dose-standardized AUC(0-12) values for MPA did not significantly differ after the concomitant administration of polysaccharide iron complex from that of the control phase (48.46 +/- 9.68 and 43.80 +/- 9.46 mg x hr/L, respectively, p=0.065). However, the AUC(0-12) for MPA significantly increased when polysaccharide iron complex was administered 2 hours after MMF (53.41 +/- 11.75 mg x hr/L, p=0.012). Maximum concentrations and times to reach maximum concentrations remained consistent across all study phases in each arm of the trial (p>0.05).


CONCLUSIONS
Multiple doses of iron therapy-slow-release ferrous sulfate, or polysaccharide iron complex-did not significantly reduce systemic exposure to MMF, as measured by using AUC(0-12) values.
Gelone
Daniele K
DK
Department of Pharmacy Practice and Administration, University of the Sciences in Philadelphia, Pennsylvania 19104-4495, USA. d.gelone@usip.edu
Park
Jeong M
JM
Lake
Kathleen D
KD
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006397:Hematinics / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000493:pharmacokinetics*; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011446:Prospective Studies
D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D006397:Hematinics; D011134:Polysaccharides; C020748:ferrous sulfate; C078972:Niferex; D007501:Iron; D009173:Mycophenolic Acid