Impairment of mycophenolate mofetil absorption by iron ion.
OBJECTIVE
We sought to evaluate the effect of iron ion on the absorption of mycophenolate mofetil, which is an immunosuppressive agent. The pharmacokinetics of mycophenolic acid were studied.


METHODS
A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the first phase, the volunteers received 1.0 g of mycophenolate mofetil alone (study 1); in the second phase, the volunteers received 1.0 g of mycophenolate mofetil and 2 tablets of iron ion preparations concomitantly (study 2). The serum concentration of mycophenolic acid, which is a pharmacologically active metabolite, was measured by reverse-phase HPLC.


RESULTS
The area under the plasma concentration-time curve from 0 to 12 hours and the maximum concentration of mycophenolic acid in study 2 were significantly less than in study 1 (area under the curve, 32.9 +/- 14.7 versus 2.92 +/- 0.883 microg x h/mL, P < .001, maximum concentration, 20.1 +/- 9.21 versus 1.30 +/- 0.367 microg x h/mL, P < .001).


CONCLUSIONS
This finding shows that when mycophenolate mofetil and iron ion preparations were administered concomitantly, a remarkable decrease of mycophenolate mofetil absorption was observed. Therefore it seems to be clear that we must avoid the concomitant administration of mycophenolate mofetil and iron ion preparations.
Morii
M
M
Department of Pharmacy and Cardiovascular Surgery, National Cardiovascular Center, Suita-city, Osaka, Japan.
Ueno
K
K
Ogawa
A
A
Kato
R
R
Yoshimura
H
H
Wada
K
K
Hashimoto
H
H
Takada
M
M
Tanaka
K
K
Nakatani
T
T
Shibakawa
M
M
D000328:Adult; D002413:Cations, Divalent; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
D002413:Cations, Divalent; D003692:Delayed-Action Preparations; D005296:Ferrous Compounds; D007166:Immunosuppressive Agents; C020748:ferrous sulfate; D009173:Mycophenolic Acid