Drug Interactions

Coadministration of CsA results in significantly lower trough concentrations of MPA (190), most likely because of diminished enterohepatic recirculation of MPAG and MPA (191). The antibiotics mycostatin, tobramycin, and cefuroxime also decrease MPA bioavailability by a similar mechanism (192). Tacrolimus may increase the bioavailability of MPA by inhibiting MPAG formation (193); however, additional studies are needed to confirm this potential drug interaction. Steroids such as dexam-ethasone lower MPA concentrations by augmenting the activity of the enzyme responsible for MPA metabolism. Several non-steroidal inflammatory drugs such as niflumic acid, diflunisal, flufenamic acid, mefenamic acid, and salicylic acid increase MPA concentrations by inhibiting MPA glucuronidation (194). Antacids (aluminum and magnesium hydroxide) lower total MPA exposure by reducing drug absorption in the gastrointestinal tract. Other drugs such as calcium polycarbophil and iron ion preparations also result in decreased MPA concentrations by the same mechanism (195). Lastly, salicylic acid and furosemide increase the free fraction of MPA by altering albumin binding.

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