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1234 PART 11: Special Problems in Critical Care
TABLE 125-9 Cytochrome P450 Classes: Selected Substrates, Inhibitors,
and Inducers
TABLE 125-9 Cytochrome P450 Classes: Selected Substrates, Inhibitors, Isozymes Substrates Inhibitors and Inducers
and Inducers (Continued)
Losartan Phenytoin
Isozymes Substrates Inhibitors and Inducers Lovastatin (3A4) Pioglitazone
Tramadol Methadone Rifabutin
Tropisetron Midazolam (3A4) Rifampin (3A4)
Venlafaxine Nelfinavir St John’s wort
Verapamil Nifedipine (3A4) Troglitazone
Zuclopenthixol Nisoldipine (3A4)
CYP2E Acetaminophen (2E1) Inhibitors Ondansetron
Chlorzoxazone (2E1) Cimetidine (2E1) Paclitaxel
Ethanol (2E1) Disulfiram (2E1) Progesterone (3A4)
Flurane anesthetics (2E1): Isoniazid (2E1) Quinidine (3A4)
Enflurane Inducers Rifabutin
Halothane Ethanol (2E1) Ritonavir
Isoflurane Isoniazid Salmeterol
Methoxyflurane Saquinavir
Sevoflurane Simvastatin
Theophylline (2E1 minor) Sirolimus (rapamycin)
CYP3A Alfentanil (3A4) Inhibitors Tacrolimus (FK506)
Alprazolam Amiodarone Tamoxifen (3A4)
Amiodarone Cimetidine (3A4) Teniposide
Amlodipine Ciprofloxacin Terfenadine (3A4)
Astemizole Clarithromycin Testosterone (3A4)
Buspirone Clotrimazole Tirilazad
Carbamazepine (3A4) Delavirdine Triazolam (3A4)
Cisapride Diltiazem Troleandomycin
Clarithromycin Erythromycin Verapamil
Clotrimazole Fluconazole (3A4) Vinblastine
Clozapine Fluvoxamine Vindesine
Codeine (minor) Grapefruit juice (naringin) (R)-Warfarin (3A4)
Cortisol Indinavir Zatosetron
Cyclobenzaprine Itraconazole (3A4) The information in this table was provided in part by Roger P. Dean, PharmD, University of Chicago Hospitals.
Cyclophosphamide Ketoconazole (3A4)
Cyclosporine Metronidazole
Phase II (conjugation) reactions form a covalent linkage between a
Dapsone (3A4) Miconazole drug’s functional group and one of a number of compounds: glucuronic
Dexamethasone Nefazodone (3A4) acid, sulfate, glutathione, acetate, or amino acids. These conjugates are
highly polar, usually inactive, and undergo urinary or fecal excretion. 49,54
Digitoxin Norfloxacin
Drug biotransformation may be enhanced or impaired by multiple
Diltiazem (3A4) Quinidine (3A4) factors, including age, gender, enzyme induction or inhibition (see
Erythromycin Ritonavir Table 125-7), pharmacogenetics, and the effects of hepatic dysfunc-
tion or other disease states (including those which decrease hepatic
Ethinyl estradiol (3A4) Saquinavir
perfusion). Conditions that impair drug biotransformation may result
Ethosuximide Sertraline (3A4) in type A adverse drug reactions, caused by accumulation of toxic con-
Etoposide (VP16) Troleandomycin centrations of parent drug or metabolites (see the section “Adverse Drug
Reactions,” below).
Felodipine (3A4) Verapamil
Granisetron Inducers Effects of Age: CYP1A2 activity is increased in children compared to
adults, causing the well-known increased theophylline dosage require-
Hydrocortisone Carbamazepine
ments in this population. 55,56 Similarly, CYP3A4 activity appears to
Imipramine (3A4) Dexamethasone (3A4) decline in the elderly compared to younger adults, 57-59 although age-
Indinavir Efavirenz related declines in hepatic size, hepatic blood flow, or drug binding and
distribution may underlie this phenomenon, because in vitro enzyme
Lansoprazole Pentobarbital
activity is unchanged with age. 60
Lidocaine (3A4) Phenobarbital
Effects of Gender: Differences in pharmacokinetic and pharmacody-
Loratadine (major) Phenylbutazone (3A4) namic properties of drugs between men and women are more commonly

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