Drug interaction between mycophenolate mofetil and tacrolimus detectable within therapeutic mycophenolic acid monitoring in renal transplant patients.
The possible pharmacokinetic interaction between the new immunosuppressive mycophenolate mofetil (MMF) and tacrolimus (TAC), respectively, was assessed by comparing routinely estimated mycophenolic acid (MPA) plasma trough levels of 15 consecutive renal transplant patients receiving MMF in combination with methylprednisolone (MEP) and cyclosporin A (CSA, 10 patients) or in combination with MEP and tacrolimus (TAC, 5 patients). Coadministration of TAC instead of CSA resulted in a significant increase of mean MPA plasma trough levels [3.4 +/- 1.3 microg/mL (n = 22) versus 1.87 +/- 1.1 microg/mL (n = 57); p < 0.001], despite lower MMF doses [1.5 +/- 0.5 g/d versus 1.7 +/- 0.3 g/d (not statistically significant)]. This elevation in MPA levels is possibly caused by an interaction between MMF and TAC and could lead to a recommendation to monitor MPA plasma levels with appropriate dose adjustment.
Hübner
G I
GI
Department of Pharmacology and Toxicology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Eismann
R
R
Sziegoleit
W
W
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000493:pharmacokinetics*
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone