Table 1. Cytochrome P450 Enzymes Involved in
the Metabolism of Foods and |
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| Isozyme | Substrate (Drug to be metabolized) |
Inhibitors of the enzyme (==> drug concentration is up) |
Inducers of the enzyme (==> drug concentration is down) |
Polymorphism1 (from the lack of enzymes to strong alleles) |
| CYP1A2 | Caffeine Theophylline: Clozapine |
Erythromycin Ciprofloxacin & Enoxacin |
Smoking Barbiturates & Carbamazepine |
Not established |
| CYP2C9 CYP2C10 CYP2C19 |
Ibuprofen2 Warfarin Omeprazole & Lansoprazole Phenytoin & Mephenytoin |
Chloramphenicol Zafirlukast & Zileuton Amiodarone Omeprazole & Cimetidine Fluoxetine & Fluvoxamine |
Rifampin Barbiturates & Carbamazepine |
CYP 2C9: rare
CYP2C29: enzyme lacking in 20% of Asians, 4 to 8% of Blacks, 3% of Caucasians |
| CYP2D6 | Codeine;
Meperidine & Methadone Propanolol & Metoprolol Flecainide Amitriptyline & Nortriptyline Desipramine Thioridazine Fluoxetine |
Quinidine
& Amiodorone Cimetidine Fluoxetine & Paroxetine Haloperidol |
CYP2D6 is not very susceptible to enzyme induction | Enzyme
lacking in 8% of Caucasians, 1% of Asians |
| CYP2E1 | Ethanol3
Acetaminophen Isoniazid3 |
Ethanol (while intoxicated) Isoniazid (while in the body) | Ethanol (when
sober) Isoniazid (when cleared out) |
Not established |
| CYP3A3 CYP3A4 CYP3A5 CYP3A6 CYP3A7 |
Terfenadine
& Astemizole Ergotamine Dapsone Saquinavir & Ritonavir Quinidine & Disopyramide Verapamil & Felodipine Lovastatin Cyclosporin & Vinca alkaloids Cisapride Birth control pills Testosterone Carbamazepine Diazepam & Midozolam Alprozolam & Triazolam |
Grapefruit
juice Erythro- & Clarithromycin Ketoconazole; Fluconazole & Itraconazole Ritonavir; Indinavir Nelfinavir & Saquinavir Delavirdine Zafirlukast Verapamil Cyclosporin Cimetidine |
Rifampin
& Rifabutin Griseofulvin Nevirapine Glucocorticosteroids Troglitazone Barbiturates & Phenytoin Carbamazepine Primidone CYP3A4 is highly susceptible to enzyme induction |
Not established |
|
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Table 2. Drugs to Be Avoided and Drugs to Be Used Carefully in Patients on Treatment for HIV-1 Infection. |
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| Avoid drugs whose high levels could be dangerous (Substrates) | Avoid the strongest CYP450 inhibitors | Avoid the strongest CYP450 inducers |
| Terfenadine
& Astemizole Theophylline Quinidine & Disopyramide & Flecainide Cisapride Ergotamine ------------------------------------------------------- Warning with these unavoidable
drugs: Opiates |
Erythromycin>Clarithromycin
(Azithromycin has no effect) Ciprofloxacin> Levofloxacin Ketoconazole>> Itraconazole>>Fluconazole Cimetidine> Other H2-blockers Ritonavir>>> Indinavir> Nelfinavir> Delavirdine> Saquinavir |
Rifampin>
rifabutin Barbiturates> Carbamazepine> Phenytoin |
Table 3. Overlapping Toxicities of Drugs Used Often in HIV-1-Infected Patients |
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Peripheral Neuropathy |
Pancreatitis |
Bone Marrow Suppression |
Renal Dysfunction |
Hepatic Dysfunction |
Didanosine (ddI) |
Didanosine Lamivudine (3TC) (Children) Pentamidine |
Zidovudine (AZT) Trimethoprim/sulfa Ganciclovir |
Aminoglycosides Amphotericin B Foscarnet Cidofovir |
Ethanol |
Table 4. Elimination Pathways of Commonly Used Drugs in HIV-1 Disease |
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| Renal excretion | Excretion through liver, bile and gut, or combined kidney and bile | Elimination through metabolic pathways |
| Zidovudine,
Stavudine, Didanosine, Zalcitabine & Lamivudine Delavirdine Sulfonamides & Trimethoprim Fluconazole & Flucytosine Acyclovir, Valacyclovir, Famciclovir, Ganciclovir, Foscarnet & Cidofovir Aminoglycosides Penicillins (most but not all) Cephalosporins (most) Imipenem & Meropenem Levofloxacin Vancomycin Ethambutol |
Saquinavir,
Indinavir, Ritonavir & Nelfinavir Nevirapine & Delavirdine* Dapsone & Pyrimethamine Atovaquone Ketoconazole & Itraconazole Nafcillin Ceftriaxone* Erythromycin, Clarithromycin, Azithromycin & Clindamycin Rifampin & Rifabutin Doxycycline & Minocycline Metronidazole Ciprofloxacin & Trovafloxacin Isoniazid |
Pentamidine Trimetrexate Amphotericin B Pyrizinamide |
| * Drugs that are dually excreted by kidneys and bile. | ||