The effect of selective bowel decontamination on the pharmacokinetics of mycophenolate mofetil in liver transplant recipients

Mycophenolate mofetil (MMF) is a prodrug immunosuppressant with a high oral bioavailability. Enterohepatic cycling of a glucuronide derivative of MMF contributes substantially to the bioavailability, but is dependent on bacte rial deglucuronidation by intestinal flora. This study aims to determine wh ether an antibiotic regimen with activity against such organisms reduces th e bioavailability of MMF by impairing enterohepatic cycling. In a prospecti ve trial, 6 liver transplant recipients were administered MMF and a 21-day antibiotic regimen for selective bowel decontamination (SBD). Time-concentr ation profiles of the pharmacologically active metabolite, mycophenolic aci d (MPA), were obtained during and after the SBD regimen. The bioavailabilit y of MPA was reduced during compared with after the regimen (14.5 +/-3.5 v 21.1 +/-9.8 mg.h/mL; P=.07). The most pronounced contribution to this reduc tion was observed from 6 hours onward (2.4 +/-1.4 v 5.6 +/-4.4 mg.h/mL; P<. 05). The presence of secondary maxima in the time-concentration profiles of MPA after, but not during, SBD indicates that enterohepatic cycling may be inhibited during SBD and restored afterward. Enterohepatic cycling may con tribute 7% to 54% (mean, 29%) of the bioavailability of MPA. We conclude th at the bioavailability of MMF may be reduced when SBD is used, and the redu ction is likely to result from the interruption of enterohepatic cycling. T his mechanism should be taken into consideration not only during SBD, but i n any clinical setting combining MMF and broad-spectrum antibiotics.