Rifampicin Cyclophosphamide

HepG2 Human hepatoblastoma Hepatocyte Cyclophosphamide (antineoplastic) Rifampicin (PXR ligand) Cytochrome P450-dependent genotoxicity Inhibition of bile acid synthesis... 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Clinically important, potentially hazardous interactions with aluminum, aminophylline, aspirin, chlorambucil, cimetidine, clarithromycin, cyclophosphamide, cyclosporine, dicumarol, diuretics, docetaxel, estrogens, grapefruit juice, indomethacin, influenza vaccines, itraconazole, ketoconazole, lansoprazole, live vaccines, methotrexate, montelukast, omeprazole, oral contraceptives, pancuronium, phenobarbital, phenytoin, ranitidine, rifampicin, rifampin, timolol, tolbutamide, vitamin A... 

Arachidonic acid, benzo[a]pyrene, carbamazepine, clozapine, cyclophosphamide, S) and (R)-ibuprofen, omeprazole, paclitaxel, progesterone, retinoic acid, sulfadiazine, temazepam, testosterone, tienilic acid, trimethoprim, (J2)-warfarin, zidovudine Sulfafenazole Rifampicin... 

Rifampicin induced the metaboiism of cyclophosphamide and ifosfamide. For ifosfamide, this did not improve the ratio of active to inactive-toxic metabolites, and the possibility remains that efficacy could be reduced. 

An in vitro study in human liver cells showed that rifampicin was a potent inducer of the activation (hydroxylation) of cyclophosphamide and... 

Rifampicin is an inducer of the cytochrome P450 isoenzymes CYP3A4 and CYP2B6, which are involved in the metabolism of cyclophosphamide and ifosfamide (see also Cyclophosphamide or Ifosfamide + Barbiturates , p.623). In the clinical study cited, rifampicin did not have a positive effect on the proportion of ifosfamide undergoing activation. In addition, since rifampicin increased metabolism overall, there is the possibility of decreased efficacy, although this remains to be shown. 

CYP2B6 is detected in human liver and is about 1-2% of total hepatic CYP. The substrates for CYP2B6 include 6-aminochrysene, methoxychlor, NNK, and cyclophosphamide. CYP2B6 in human primary hepatocytes is typically induced by PB and rifampicin through the nuclear receptor CAR (constitu-tively active receptor) (Sueyoshi et al., 1999) and probably also by PXR... 

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