scholarly journals Molecular Basis of Cardiovascular Drug Metabolism : Implications for Predicting Clinically Important Drug Interactions

Circulation ◽  
2000 ◽  
Vol 101 (14) ◽  
pp. 1749-1753 ◽  
Author(s):  
D. R. Abernethy ◽  
D. A. Flockhart
Keyword(s):  
Drug Metabolism ◽  
Drug Interactions ◽  
Molecular Basis ◽  
Cardiovascular Drug ◽  
Important Drug

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

2019 ◽  
Vol 18 (23) ◽  
pp. 2042-2055 ◽  
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.

Food and drugs

2002 ◽  
Vol 55 (1-2) ◽  
pp. 5-12 ◽  
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.

scholarly journals In Silico Prediction of Drug–Drug Interactions Mediated by Cytochrome P450 Isoforms

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 538
Author(s):  
Alexander V. Dmitriev ◽  
Anastassia V. Rudik ◽  
Dmitry A. Karasev ◽  
Pavel V. Pogodin ◽  
Alexey A. Lagunin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Cytochromes P450 ◽  
Investigational Drug ◽  
Web Resource ◽  
Average Accuracy ◽  
Structural Formulas ◽  
Cytochrome P450 Isoforms ◽  
Leave One Out ◽  
Important Drug

Drug–drug interactions (DDIs) can cause drug toxicities, reduced pharmacological effects, and adverse drug reactions. Studies aiming to determine the possible DDIs for an investigational drug are part of the drug discovery and development process and include an assessment of the DDIs potential mediated by inhibition or induction of the most important drug-metabolizing cytochrome P450 isoforms. Our study was dedicated to creating a computer model for prediction of the DDIs mediated by the seven most important P450 cytochromes: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2D6, and CYP3A4. For the creation of structure–activity relationship (SAR) models that predict metabolism-mediated DDIs for pairs of molecules, we applied the Prediction of Activity Spectra for Substances (PASS) software and Pairs of Substances Multilevel Neighborhoods of Atoms (PoSMNA) descriptors calculated based on structural formulas. About 2500 records on DDIs mediated by these cytochromes were used as a training set. Prediction can be carried out both for known drugs and for new, not-yet-synthesized substances. The average accuracy of the prediction of DDIs mediated by various isoforms of cytochrome P450 estimated by leave-one-out cross-validation (LOO CV) procedures was about 0.92. The SAR models created are publicly available as a web resource and provide predictions of DDIs mediated by the most important cytochromes P450.

scholarly journals Hierarchy of evidence in interpretation of clinical significance of drug interactions

2012 ◽  
Vol 65 (1-2) ◽  
pp. 45-49
Author(s):  
Bozana Nikolic ◽  
Miroslav Savic
Keyword(s):  
Drug Metabolism ◽  
Drug Interactions ◽  
Clinical Significance ◽  
Health Professionals ◽  
Molecular Entity ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Potential Interactions

Introduction. Since drug interactions may result in serious adverse effects or failure of therapy, it is of huge importance that health professionals base their decisions about drug prescription, dispensing and administration on reliable research evidence, taking into account the hierarchy of data sources for evaluation. Clinical Significance of Potential Interactions - Information Sources. The sources of data regarding drug interactions are numerous, beginning with various drug reference books. However, they are far from uniformity in the way of choosing and presenting putative clinically relevant interactions. Clinical Significance of Potential Interactions - Interpretation of Information. The difficulties in interpretation of drug interactions are illustrated through the analysis of a published example involving assessment made by two different groups of health professionals. Systematic Evaluation of Drug-Drug Interaction. The potential for interactions is mainly investigated before marketing a drug. Generally, the in vitro, followed by in vivo studies are to be performed. The major metabolic pathways involved in the metabolism of a new molecular entity, as well as the potential of induction of human enzymes involved in drug metabolism are to be examined. In the field of interaction research it is possible to make use of the population pharmacokinetic studies as well as of the pharmacodynamic assessment, and also the postregistration monitoring of the reported adverse reactions and other literature data. Conclusion. In vitro and in vivo drug metabolism and transport studies should be conducted to elucidate the mechanisms and potential for drug-drug interactions. The assessment of their clinical significance should be based on well-defined and validated exposure-response data.

Clinically important drug interactions

Reactions ◽  
1988 ◽  
Vol 215 (1) ◽  
pp. 3-4
Keyword(s):  
Drug Interactions ◽  
Important Drug

Principles of Clinically Important Drug Interactions with Carbamazepine. Part II

1991 ◽  
Vol 11 (5) ◽  
pp. 306???312
Author(s):  
TERENCE A. KETTER ◽  
ROBERT M. POST ◽  
KATHY WORTHINGTON
Keyword(s):  
Drug Interactions ◽  
Important Drug
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