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Mini Review Special Issue Lymphology & Phlebology
Drug disposition in diseases altering cyp450-mediated metabolism
Noha A Hamdy, Sahar K Hegazy, Ahmed G Adam, Nawal MK halafallah
Received: January 01, 1971 | Published: November 26, 2018
Citation: Hamdy NA, Hegazy SK, Adam AG, et al. Drug disposition in diseases altering cyp450-mediated metabolism. MOJ Immunol. 2018;6(6):267-273. DOI: 10.15406/moji.2018.06.00241
Abstract
Drug-disease interaction should be considered in drug prescribing, as some inflammatory diseases down regulate CYP activities and thus may alter drug disposition, especially for autoimmune diseases. Many studies either in animals or humans demonstrated the effect of inflammatory mediators released during inflammation or infection on drug metabolism, circulating cytokines depress cytochrome P-450 enzymes activities which are responsible for the metabolism of many drugs. These drugs may include drugs used for the control of these diseases per se. Also, several organisms have been reported to alter P450-mediated metabolism by inoculating the organisms or their lipopolysaccharides in laboratory animals either peritoneally, intra cerebroventricularly or orally.
The mechanism of inhibition was suggested and proved in some studies to be related to inflammatory cytokines such as IL-6 and TNF-α, IL-1β and IFN-γ and C-reactive protein (CRP), another proposed mechanism involves nitric oxide (NO) production as an inhibitory intermediate released from cytokines to inhibit CYP-450 enzymes.
Start of inhibition time varies from 12hrs to 24hrs depending on cytokines release in inflammatory disease or 2-8 days in infection related to the time of release of inflammatory mediators. The percentage of inhibition varied from 40-60%.
Type of inflammatory disease and degree of inflammation will differently affect CYP metabolism. The data generated stress the importance of monitoring drug level or clinical response during episodes of infection or inflammation. Limited number of studies showing induction of CYP-450 was also discussed. Regarding human studies, similar studies were also reported to alter CYP-450 metabolism during infection episodes. To conclude, care should be taken in patients with inflammatory diseases concerning drug dose adjustment which may be required according to severity and duration of disease and depending on safety profile of the drug.
Keywords: Inflammation, Infection, Drug disease interaction, CYP-450 metabolism, Inflammatory mediators, Cytokines Aryl Hydrocarbon Receptor, Nuclear Translocator, Cecal Ligation and Puncture, Coxsackievirus, C-Reactive Protein, Cytochrome P-450, Ethoxycoumarin O-Deethylase, Growth Hormone,m Imipramine N-Demethylase, inducible Nitric Oxide Synthetase, intracerebroventricularly, Interferon ?,
©2018 Hamdy, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.
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