ArticleAlcoholism, clinical and experimental research2011
Differential effects of ethanol on spectral binding and inhibition of cytochrome P450 3A4 with eight protease inhibitors antiretroviral drugs.
Article in Alcoholism, clinical and experimental research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Effectiveness of naltrexone treatment for alcohol use disorders in HIV: a systematic review.Substance abuse treatment, prevention, and policy · 2020Pooled it
- Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response.Scientific reports · 2023Article
- An update on drug-drug interactions between antiretroviral therapies and drugs of abuse in HIV systems.Expert opinion on drug metabolism & toxicology · 2020Review
- Choosing the right pharmacotherapeutic strategy for HIV maintenance in patients with alcohol addiction.Expert opinion on pharmacotherapy · 2019Article
- Antiretroviral Therapy and Alcohol Interactions: X-raying Testicular and Seminal Parameters Under the HAART Era.European journal of drug metabolism and pharmacokinetics · 2018Review
- Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies.Pharmaceutical research · 2017Article
- Alcohol use disorders among people living with HIV/AIDS in Southern Brazil: prevalence, risk factors and biological markers outcomes.BMC infectious diseases · 2017Article
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- Investigational protease inhibitors as antiretroviral therapies.Expert opinion on investigational drugs · 2016Review
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- Effect of Methamphetamine on Spectral Binding, Ligand Docking and Metabolism of Anti-HIV Drugs with CYP3A4.PloS one · 2016Article
- Chronic Effects of Ethanol and/or Darunavir/Ritonavir on U937 Monocytic Cells: Regulation of Cytochrome P450 and Antioxidant Enzymes, Oxidative Stress, and Cytotoxicity.Alcoholism, clinical and experimental research · 2016Article
- Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.Expert opinion on drug metabolism & toxicology · 2015Review
- Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1.Current drug metabolism · 2015Review
- HIV-1, HCV and alcohol in the CNS: potential interactions and effects on neuroinflammation.Current HIV research · 2014Review
- Alcohol abuse and HIV infection: role of DRD2.Current HIV research · 2014Article
- Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes.Expert opinion on drug metabolism & toxicology · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCytochrome P450 3A4 (CYP3A4) is the most abundant CYP enzyme in the liver, which metabolizes approximately 50% of the marketed drugs including antiretroviral agents. CYP3A4 induction by ethanol and its impact on drug metabolism and toxicity is known. However, CYP3A4-ethanol physical interaction and its impact on drug binding, inhibition, or metabolism is not known, except that we have recently shown that ethanol facilitates the binding of a protease inhibitor (PI), nelfinavir, with CYP3A4. The current study was designed to examine the effect of ethanol on spectral binding and inhibition of CYP3A4 with all currently used PIs that differ in physicochemical properties.
methodsWe performed type I and type II spectral binding with CYP3A4 at 0 and 20 mM ethanol and varying PIs' concentrations. We also performed CYP3A4 inhibition using 7-benzyloxy-4-trifluoromethylcoumarin substrate and NADPH at varying concentrations of PIs and ethanol.
resultsAtazanavir, lopinavir, saquinavir, and tipranavir showed type I spectral binding, whereas indinavir and ritonavir showed type II. However, amprenavir and darunavir did not show spectral binding with CYP3A4. Ethanol at 20 mM decreased the maximum spectral change (δA(max)) with type I lopinavir and saquinavir, but it did not alter δA(max) with other PIs. Ethanol did not alter spectral binding affinity (K(D)) and inhibition constant (IC(50)) of type I PIs. However, ethanol significantly decreased the IC(50) of type II PIs, indinavir and ritonavir, and markedly increased the IC(50) of amprenavir and darunavir.
conclusionsOverall, our results suggest that ethanol differentially alters the binding and inhibition of CYP3A4 with the PIs that have different physicochemical properties. This study has clinical relevance because alcohol has been shown to alter the response to antiretroviral drugs, including PIs, in HIV-1-infected individuals.
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