Impairment of Mycophenolate Mofetil Absorption by Calcium Polycarbophil

• Published in: Journal of clinical pharmacology 2002-11, Vol.42 (11), p.1275-1280
• Main Authors: Kato, Ryuji, Ooi, Kazuya, Ikura-Morii, Megumi, Tsuchishita, Yoshimasa, Hashimoto, Hiroshi, Yoshimura, Hironori, Uenishi, Kohji, Kawai, Masayuki, Tanaka, Kazuhiko, Ueno, Kazuyuki
• Format: Article
• Language: English
• Subjects: Absorption; Acrylic Resins - pharmacology; Administration, Oral; Adult; Area Under Curve; Biological and medical sciences; Calcium Chloride - chemistry; Cations; Cellulose - chemistry; Chelating Agents - pharmacology; Cross-Over Studies; Drug Antagonism; Ferrous Compounds - chemistry; Humans; Immunomodulators; Immunosuppressive Agents - blood; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - pharmacokinetics; Male; Medical sciences; Membranes, Artificial; Middle Aged; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; Mycophenolic Acid - chemistry; Mycophenolic Acid - pharmacokinetics; Pharmacology. Drug treatments; Time Factors
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/009127002762491389

The effect of calcium polycarbophil on the absorption of mycophenolate mofetil, an immunosuppressive agent, was evaluated in healthy subjects. In vitro studies were performed to further evaluate the mechanism of the potential interaction. In the in vitro study, the release of mycophenolate mofetil from a cellulose membrane in the presence orabsence of metal cations was measured using the dissolution test procedure. In the in vivo study, a randomized crossover design with two phases was used. In one phase, 6 male healthy volunteers received 1000 mg of mycophenolate mofetil alone (treatment 1); in the other phase, they received 1000 mg of mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 2). They received 30 mg of lansoprazole for 5 days and, on the 6th day, received mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 3). The serum concentration of mycophenolic acid was measured by high‐performance liquid chromatography. In the in vitro study, the release from a cellulose membrane in the presence of calcium or iron ions was slower than that in the absence of these metal ions. In the in vivo study, the AUC0–12 and Cmax in treatment 2 were less than those in treatment 1. About 50% and 25% decreases in AUC0–12 in treatment 2 and treatment 3 were observed compared with those in treatment 1, respectively. These findings suggest that when mycophenolate mofetil and calcium polycarbophil were coadministered concomitantly, a decrease in mycophenolate mofetil absorption was observed. Therefore, it appears clear that the concomitant administration of mycophenolate mofetil and calcium polycarbophil should be avoided.