Oral antibiotics lower mycophenolate mofetil drug exposure, possibly by interfering with the enterohepatic recirculation: A case series

Abstract

Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic coadministration. By diminishing gut bacteria β‐glucuronidase activity, oral antibiotics can prevent deglucuronidation of the inactive MPA‐7‐O‐glucuronide metabolite to MPA and thereby possibly prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, and pragmatic close monitoring of the MPA exposure in cases is advised.

Pharmacomicrobiomics of Classical Immunosuppressant Drugs: A Systematic Review

“…Importantly, Simpson et al [ 33 ] showed that the most important predictive factor for MPAG reactivation in the gut was the presence of GUS producing bacteria. The effect of intestinal bacteria on MPA pharmacokinetics could be clinically relevant as suggested by a study published after we finished our literature search, which showed a substantial decrease in MPA exposure in a very small case series of patients with signs of immunosuppressive therapy failure after starting an antibiotic treatment [ 122 ]. A paper by Guo et al (2019) [ 25 ] examined the ability of intestinal bacteria to metabolize TAC and showed that Faecalibacterium prausnitzii converts this cIMD into a C-9 keto-reduction product, the M1 metabolite, which is approximately 15-fold less potent than the parent drug.…”