Identification of Cytochrome P450-Mediated Drug–Drug Interactions at Risk in Cases of Gene Polymorphisms by Using a Quantitative Prediction Model

2018 ◽  
Vol 57 (12) ◽  
pp. 1581-1591 ◽  
Author(s):  
Nicolas Fermier ◽  
Laurent Bourguignon ◽  
Sylvain Goutelle ◽  
Nathalie Bleyzac ◽  
Michel Tod
Keyword(s):  
At Risk ◽  
Cytochrome P450 ◽  
Prediction Model ◽  
Drug Interactions ◽  
Gene Polymorphisms ◽  
Quantitative Prediction

Quantitative Prediction of Cytochrome P450 (CYP) 2D6-Mediated Drug Interactions

2011 ◽  
Vol 50 (8) ◽  
pp. 519-530 ◽  
Author(s):  
Michel Tod ◽  
Sylvain Goutelle ◽  
Fannie Clavel-Grabit ◽  
Grégoire Nicolas ◽  
Bruno Charpiat
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Quantitative Prediction ◽  
Cyp 2D6

scholarly journals In Vivo Quantitative Prediction of the Effect of Gene Polymorphisms and Drug Interactions on Drug Exposure for CYP2C19 Substrates

2013 ◽  
Vol 15 (2) ◽  
pp. 415-426 ◽  
Author(s):  
Sylvain Goutelle ◽  
◽  
Laurent Bourguignon ◽  
Nathalie Bleyzac ◽  
Johanna Berry ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Gene Polymorphisms ◽  
Drug Exposure ◽  
Quantitative Prediction

Quantitative Prediction of the Impact of Drug Interactions and Genetic Polymorphisms on Cytochrome P450 2C9 Substrate Exposure

2013 ◽  
Vol 52 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Anne-Charlotte Castellan ◽  
◽  
Michel Tod ◽  
François Gueyffier ◽  
Mélanie Audars ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Genetic Polymorphisms ◽  
Quantitative Prediction ◽  
Cytochrome P450 2C9 ◽  
The Impact

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.

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 In vitro inhibition of human cytochrome P450 enzymes by the novel atypical antipsychotic drug asenapine: a prediction of possible drug–drug interactions

2020 ◽  
Vol 72 (3) ◽  
pp. 612-621 ◽  
Author(s):  
Jacek Wójcikowski ◽  
Przemysław J. Danek ◽  
Agnieszka Basińska-Ziobroń ◽  
Renata Pukło ◽  
Władysława A. Daniel
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Atypical Antipsychotic ◽  
Antipsychotic Drug ◽  
The Novel ◽  
Cytochrome P450 Enzymes ◽  
Atypical Antipsychotic Drug ◽  
Human Cytochrome ◽  
In Vitro Inhibition

Cardiovascular, Dermatological, Gastrointestinal, Hematological, Hormonal, and Immunosuppressant Agents

2002 ◽  
Vol 37 (10) ◽  
pp. 1113-1126 ◽  
Author(s):  
Joyce A. Generali
Keyword(s):  
At Risk ◽  
Adverse Events ◽  
Drug Interactions ◽  
Prescription Drugs ◽  
Hospital Pharmacy ◽  
Safety Data ◽  
Black Box ◽  
Information Monitoring ◽  
Black Box Warnings ◽  
Wall Chart

“Black-box” warnings report valuable postmarketing safety data about prescription drugs, keeping practitioners informed about potential adverse events, drug interactions, key dosing information, monitoring and administration requirements, and at-risk patient populations. They are especially crucial for newly approved agents. A list of agents with black-box warnings does not currently exist; however Hospital Pharmacy will be publishing comprehensive lists by drug category in this column until November 2002. At that time, a complete list in wall chart form will be released. Hospital Pharmacy will update the data as salient information becomes available.

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