Effects of twenty-three drugs on the metabolism of FK506 by human liver microsomes.
We investigated the effects of 23 drugs on the metabolism of FK506 by human liver microsomes. Acyclovir, amphotericin B, cefixime, cefotaxime, ciprofloxacin, cyclosporin A, diltiazem, enoxacin, erythromycin, ethinyl estradiol, fluconazole, fosfomycin, kanamycin, lincomycin, loxoprofen, minocyclin, nifedipine, nilvadipine, norethindrone, ofloxacin, phenobarbital, prednisolone, or rifampicin was added to the reaction media at equimolar or at ten times an excess molar ratio of the substrate concentration; their effects on FK506 metabolism were examined. Drugs known to be the substrate of cytochrome P-450 3A inhibited the metabolism of FK506, and among the drugs tested, the inhibition by cyclosporin A and nifedipine was the strongest.
Iwasaki
K
K
Department of Pharmacokinetics and Drug Metabolism, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Matsuda
H
H
Nagase
K
K
Shiraga
T
T
Tokuma
Y
Y
Uchida
K
K
D000890:Anti-Infective Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D016559:Tacrolimus / Q000378:metabolism*
D000890:Anti-Infective Agents; D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D016559:Tacrolimus