Rifampin induces alterations in mycophenolic acid glucuronidation and elimination: Implications for drug exposure in renal allograft recipients

Abstract

This study demonstrates an interaction between mycophenolate mofetil and rifampin, which is a result of induction of MPA glucuronidation and possibly also rifampin-associated alterations in MRP2-mediated transport of MPAG and AcMPAG. This interaction should be taken into account when rifampin or other drugs influencing pregnane X receptor activity are coadministered with mycophenolate mofetil.

Therapeutic Drug Monitoring of Mycophenolic Acid

“…Agents such as corticosteroids and rifampin (16), when introduced into the regimen, stimulate the biosynthesis of UGT, thereby increasing MPA clearance with consequent decreased MPA concentration. Discontinuation of such inducing drugs reduces MPA clearance and consequently increases MPA concentrations.…”

Contribution of N-Glucuronidation to Efavirenz Elimination In Vivo in the Basal and Rifampin-Induced Metabolism of Efavirenz

“…However, a major concern of such a combination has been rifampin's ability to induce multiple drug-metabolizing enzymes and drug transporters, which results in the altered disposition of many coadministered drugs (24). Evidence exists that rifampin enhances the metabolism of UGT substrates, such as mycophenolic acid (23) and zidovudine (2,10). However, the effect of rifampin on the rate of N-glucuronidation of efavirenz remains unknown.…”

Legemiddelinteraksjoner og immunsuppresjon hos organtransplanterte

“…Dette legemidlet bremser proliferasjonen av aktiverte lymfocytter ved å hemme syntesen av (deoksy)guaninnukleotider (29). Aktuelle legemiddelinteraksjoner for mykofenolat er oppsummert i tabell 2 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43).…”

“…Det er også rapportert at tuberkulostatisk behandling med rifampicin medfører redusert mykofenolatnivå (36,37). Rifampicin induserer uttrykket av glukuronosyltransferaser slik at glukuronideringen av mykofenolat øker (36,46).…”

“…Rifampicin induserer uttrykket av glukuronosyltransferaser slik at glukuronideringen av mykofenolat øker (36,46). Fenobarbital, fenytoin, karbamazepin (7) Rifampicin (6,7,10) Erytromycin, klaritromycin (6-10, 13, 14) Johannesurt (Hypericum perforatum) 1 (6) Diltiazem, verapamil (6)(7)(8)(9)(10)(15)(16)(17)(18) Indinavir, ritonavir (6,8) Grapefruktjuice 2 (8,9) Ciklosporin ⇒ økt systemisk nivå av sirolimus og everolimus (10,19) Orlistat ⇒ redusert absorpsjon og systemisk nivå av ciklosporin 3 (20) Sirolimus, everolimus ⇒ økt lokalt nivå av ciklosporin og takrolimus i nyrevev kan gi økt nefrotoksisitet (21) 1 Naturlegemiddel 2 Naeringsmiddel 3 Ikke relatert til induksjon av CYP3A4 eller P-gp…”