THE ROLE OF DRUG METABOLISM IN THE DEVELOPMENT OF CLINICALLY SIGNIFICANT ADVERSE DRUG INTERACTIONS

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.

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The Role of Metabonomics at the Interface Between Drug Metabolism and Safety Assessment

Current Drug Metabolism ◽

10.2174/138920010794233512 ◽

2010 ◽

Vol 11 (8) ◽

pp. 686-692 ◽

Cited By ~ 9

Author(s):

Nigel J. Waters

Keyword(s):

Drug Metabolism ◽

Safety Assessment

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Biology of Heme: Drug Interactions and Adverse Drug Reactions with CYP450

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666181129124638 ◽

2019 ◽

Vol 18 (23) ◽

pp. 2042-2055 ◽

Cited By ~ 4

Author(s):

Neeraj Kumar ◽

Heerak Chugh ◽

Damini Sood ◽

Snigdha Singh ◽

Aarushi Singh ◽

...

Keyword(s):

Cytochrome P450 ◽

Drug Metabolism ◽

Drug Interactions ◽

Adverse Drug Reactions ◽

Genetic Defects ◽

Drug Reactions ◽

Detailed Structure ◽

Synthesis And Degradation ◽

Porphyrin Rings

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.

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Food and drugs

Medicinski pregled ◽

10.2298/mpns0202005d ◽

2002 ◽

Vol 55 (1-2) ◽

pp. 5-12 ◽

Cited By ~ 1

Author(s):

Kornelija Djakovic-Svajcer

Keyword(s):

Plasma Level ◽

Drug Metabolism ◽

Drug Interactions ◽

Therapeutic Effect ◽

Significant Influence ◽

Plasma Concentrations ◽

Chemical Properties ◽

Therapeutic Index ◽

Food Composition ◽

Drug Bioavailability

Food can exert a significant influence on the effects of certain drugs. The interactions between food and drugs can be pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions most often take place on absorption and drug metabolism levels. Absorption can be either accelerated or delayed, increased or decreased, while drug metabolism can be either stimulated or inhibited. The factors which influence food-drug interactions are as follows: composition and physic-chemical properties of drugs, the interval between a meal and drug intake and food composition. Food consistency is of lesser influence on drug bioavailability than food composition (proteins, fats, carbohydrates, cereals). Important interactions can occur during application of drugs with low therapeutic index, whereby the plasma level significantly varies due to changes in resorption or metabolism (e.g. digoxin, theophyllin, cyclosporin) and drugs such as antibiotics, whose proper therapeutic effect requires precise plasma concentrations.

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Alcohol Use Disorder

10.1093/oso/9780190676001.003.0005 ◽

2018 ◽

Author(s):

Igor Ponomarev

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Critical Discussion ◽

Epigenetic Mechanisms ◽

Future Directions ◽

Clinically Significant ◽

Early Life Exposures ◽

The Brain ◽

Epigenetic Research

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.

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Drug interactions: a review of the unseen danger of experimental COVID-19 therapies

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa340 ◽

2020 ◽

Vol 75 (12) ◽

pp. 3417-3424 ◽

Cited By ~ 1

Author(s):

Catherine Hodge ◽

Fiona Marra ◽

Catia Marzolini ◽

Alison Boyle ◽

Sara Gibbons ◽

...

Keyword(s):

Drug Interactions ◽

Herbal Medicines ◽

Qt Prolongation ◽

Critically Ill Patient ◽

Experimental Drugs ◽

Mesh Terms ◽

Experimental Therapies ◽

Clinically Significant ◽

Novel Coronavirus

Abstract As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

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