Drug interactions cytochrome

Sagir A, Schmitt M, Dilger K, Haussinger D (2003) Inhibition of cytochrome P450 3A relevant drug interactions in gastroenterology. Digestion 68 41 8... 

Many cytochrome P450s are inducible. This has important implications in phenomena such as drug interaction. 

Lewis, D. F., Lake, B. G., Ito, Y., Anzenbacher, P. Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes the importance of lipophilicity for binding and metabolism. Drug Metab. Drug Interact. 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Several antidepressants, including most of the SSRIs, nefa-zodone, and duloxetine, are known to inhibit various cytochrome P-450 isoenzymes, thereby elevating plasma levels of substrates for those isoenzymes and thus potentially leading to increased adverse effects or toxicity of those drugs. The propensity to cause these drug interactions will vary with the particular antidepressant and the precise isoenzyme9,19,30 (Table 35-6). 

Ethinyl estradiol is metabolized in the liver via the cytochrome P-450 system. It is metabolized primarily via CYP450 3A4. When reviewing drug interactions of oral contraceptives, it is important to keep in mind that antibiotic administration during contraceptive use may decrease the efficacy of many combined contraceptives. Refer to Table 45-4 for a list of common drug interactions seen with oral contraceptives.1,31... 

The use of duloxetine in stress urinary incontinence is complicated by (1) the potential for multiple clinically relevant drug-drug interactions with cytochrome P-450 2D6 and 1A2 inhibitors, (2) withdrawal reactions if abruptly discontinued, (3) high rates of nausea and other side effects, (4) the hepa-totoxicity that contraindicates its use in patients with any degree of hepatic impairment, and (5) its mild hypertensive effect. 

Clarithromycin 15 mg/kg per day in 2 doses (adult 250 mg twice daily) Diarrhea, vomiting, rash, abnormal taste, abdominal pain SJ Many drug interactions (inhibits cytochrome P-450 3A4) suspension cannot be refrigerated and has metallic taste same microbiologic issues as azithromycin... 

Jones, B. C., Ciark, S. E., Human cytochromes P450 and their role in metabolism based drug-drug interactions, in Drug-Drug Interactions. Rodrigues, A. D. (ed.), 2001, Chapter 3, 55-88. Marcel Dekker Inc. New York. 

Lampen, A., Christians, U., Guengerich, F. P., Watkins, P. B., Koiars, J. C., Bader, A., Dralle, H., Hackbarth, I., Sewing, K. F., Metabolism of the immunosuppressant tacrolimus in the small intestine cytochrome P450 drug interactions, and interindividual variability, Drug Metab. Disp. 1995, 23, 1315-1324. 

Labroo, R. B., Paine, M. F., Thummel, K. E., Kharasch, E. D., Fentanyl metabolism by human hepatic and intestinal cytochrome P4503A4. Implications for interindividual variability in disposition, efficacy and drug interactions, Drug Metab. Disp. 1997, 25, 1072-1080. 

The answer is d. (Kai ung, p 505.) Fluoxetine is a highly selective serotonin re uptake inhibitor (55RI) acting on the 5-1 IT transporter. It forms an active metabolite that is effective for several days. Selective serotonin reuptake inhibitors are inhibitors of cytochrome P450 isoenzymes, which is the basis of potential drug-drug interactions... 

The ability of an SSRI, or any antidepressant, to inhibit or induce the activity of the cytochrome P450 (CYP450) enzymes can be a significant contributory factor in determining its capability to cause a pharmacokinetic drug-drug interaction. 

To avoid drug interactions, clinicians should be careful when administering duloxetine with substrates or inhibitors of cytochrome P450 (CYP450) isoenzymes 2D6 and 1A2. 

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