Nifedipine Erythromycin

Wrighton, S.A. Ring, B.J. Inhibition of human CYP3A catalyzed I -hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine. Pharm.Res., 1994, 11, 921-924... 

FIGURE 4.20 Structures of the CYP3A4 substrates, erythromycin, nifedipine, testosterone, and midazolam, and their metabolites. 

Cardiac depressant effects may occur when verapamil or diltiazem is combined with a (p-adrenoceptor antagonoist or a cardiac glycoside. Nifedipine and verapamil are metabolised by cytochrome P-450 3A4. Inhibitors of this enzyme, e.g. HIV-protease inhibitors, cimetidine, fluoxetine, ketoconazole, erythromycin, will increase plasma levels and the dose should be carefully monitored. Conversely, enzyme inducers, e.g. carbamazepine, rifampicin, phenytoin, will decrease their plasma concentrations. 

A4 Nifedipine, ethylmorphine, warfarin, quinidine, taxol, ketoconazole, verapamil, erythromycin, diazepam Aflatoxin, 1-nitropyrene, benzo(a)pyrene 7,8-diol, 6 aminochrysene, estradiol, progesterone, testosterone, other steroids, bile acids Erythromycin, nifedipine [testosterone (6-/3)]... 

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

A4 Midazolam, Testosterone (strongly recommended to use at least two structurally unrelated substrates) Nifedipine, Felodipine, Cyclosporine, Terfenadine, Erythromycin, Simvastatin Ketoconazole (recent evidence that it is also a potent inhibitor of 2C8), Troleandomycin Cyclosporine... 

The most used and validated probe drugs for C YP3 A phenotyping are midazolam and 14C-erythromycin (Watkins 1994). Alfentanyl, alprazolam, dapsone, dextromethorphan, lidocaine. nifedipine, omeprazole, quinine, verapamil have also been used but less frequently, and CYP3A specificity for some of them has been questioned. The endogenous 6(->-hydroxycortisol test (measurement of 6 3-hydroxycortisol cortisol ratio in urine) is only useful for detecting CYP3A induction, and may be influenced by renal CYP3 A activity. 

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

Tamoxifen is absorbed orally, with peak concentrations in 4-7 h, biphasic decline in plasma concentration, and a terminal half-life of 7 days. The predominant metabolite is N-desmethyltamoxifen, which has a half-life of 14 days. However, a minor metabolite, 4-hydroxytamoxifen, is also generated. Both of these are further metabolized to 4-hydroxy-N-desmethylta-moxifen. In vitro studies showed that erythromycin, cyclosporin, nifedipine, and kiltiazem competitively inhibited formation of the latter metabolite. Steady-state levels are achieved after approximately 4 weeks of treatment. Tamoxifen is enterohepatically recirculated and excreted primarily in the stool. 

Benzodiazepines alprazolam, clonazepam, diazepam, midazolam, triazolam, zolpidem Calcium channel blockers diltiazem, nifedipine, nimodipine, verapamil Steroids androgens, estrogens, cortisol Others erythromycin, terfenadine, cyclosporine, dapsone, ketoconazole, lovastatin, lidocaine, alfentanil, amiodarone, astemizole, codeine, sildenafil... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

Clinically important, potentially hazardous interactions with cimetidine, cyclosporine, erythromycin, ketoconazole, nifedipine... 

CYP3A3/4 Cyclosporine Verapamil Nifedipine blockers Phenytoin Rifampin Barbiturates Erythromycin Verapamil Ketoconazole Grapefruit juice (Yes)" Erythromcyin Midazolam... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Midazolam, testosterone, nifedipine, felodipine, cyclosporine, terfenadine, erythromycin, simvastatin... 

Yamazaki, H., Urano, T, Hiroki, S., and Shimada, T. (1996). Effects of erythromycin and roxithromycin on oxidation of testosterone and nifedipine catalyzed by CYP3A4 in human liver microsomes. J. Toxicol. Scl. 21, 215-226. 

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