In Silico Predictions and In Vivo Results of Drug-Drug Interactions by Ketoconazole and Verapamil on AZD1305, a Combined Ion Channel Blocker and a Sensitive CYP3A4 Substrate

2016 ◽  
Vol 5 (5) ◽  
pp. 364-373 ◽  
Author(s):  
Susanne Johansson ◽  
Boel Löfberg ◽  
Maria Aunes ◽  
Helen Lunde ◽  
Lars Frison ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Ion Channel ◽  
In Silico ◽  
Channel Blocker ◽  
Cyp3a4 Substrate ◽  
In Silico Predictions

scholarly journals In silico predictions; in vivo veritas

10.1038/9833 ◽  
1999 ◽  
Vol 17 (6) ◽  
pp. 533-534 ◽  
Author(s):  
Anne S. De Groot ◽  
Frank G. Rothman
Keyword(s):  
In Silico ◽  
In Silico Predictions

scholarly journals Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 566
Author(s):  
Bonifasius Putera Sampurna ◽  
Fiorency Santoso ◽  
Jia-Hau Lee ◽  
Wen-Hao Yu ◽  
Chin-Chung Wu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Ion Channel ◽  
In Silico ◽  
Docking Simulation ◽  
Docking Studies ◽  
Zebrafish Model ◽  
Critical Issues ◽  
Domain Iii

Safety is one of the most important and critical issues in drug development. Many drugs were abandoned in clinical trials and retracted from the market because of unknown side effects. Cardiotoxicity is one of the most common reasons for drug retraction due to its potential side effects, i.e., inducing either tachycardia, bradycardia or arrhythmia. The zebrafish model could be used to screen drug libraries with potential cardiotoxicity in a high-throughput manner. In addition, the fundamental principles of replacement, reduction, and refinement of laboratory animal usage, 3R, could be achieved by using zebrafish as an alternative to animal models. In this study, we used a simple ImageJ-based method to evaluate and screen 70 ion channel ligands and successfully identify six compounds with strong cardiotoxicity in vivo. Next, we conducted an in silico-based molecular docking simulation to elucidate five identified compounds that might interact with domain III or domain IV of the Danio rerio L-type calcium channel (LTCC), a known pharmaceutically important target for arrhythmia. In conclusion, in this study, we provide a web lab and dry lab combinatorial approach to perform in vivo cardiotoxicity drug screening and in silico mechanistic studies.

scholarly journals Comparing in vivo data and in silico predictions for acute effects assessment of biocidal active substances and metabolites for aquatic organisms

2020 ◽  
Vol 205 ◽  
pp. 111291
Author(s):  
María Blázquez ◽  
Oscar Andreu-Sánchez ◽  
Irati Ranero ◽  
María Luisa Fernández-Cruz ◽  
Emilio Benfenati
Keyword(s):  
In Silico ◽  
Aquatic Organisms ◽  
Acute Effects ◽  
In Silico Predictions ◽  
Active Substances ◽  
Effects Assessment

Solidified SNEDDS of loratadine: formulation using hydrophilic and hydrophobic grades of Aerosil®, pharmacokinetic evaluations and in vivo–in silico predictions using GastroPlus™

RSC Advances ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 3099-3116 ◽  
Author(s):  
Samridhi Verma ◽  
Sandeep Kumar Singh ◽  
Priya Ranjan Prasad Verma
Keyword(s):  
In Silico ◽  
In Silico Predictions ◽  
Biopharmaceutical Properties

Hydrophilic and hydrophobic grades of Aerosil® were employed to develop solid-SNEDDS of loratadine and evaluated for their influence on powder, physicochemical and biopharmaceutical properties.

scholarly journals Evaluation of Pharmacokinetic Drug–Drug Interactions: A Review of the Mechanisms, In Vitro and In Silico Approaches

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 75
Author(s):  
Yaru Peng ◽  
Zeneng Cheng ◽  
Feifan Xie
Keyword(s):  
Drug Interactions ◽  
In Silico ◽  
Drug Efficacy ◽  
Primary Concern ◽  
Factors Affecting ◽  
Pbpk Models ◽  
Drug Concentrations ◽  
Pharmacokinetic Drug

Pharmacokinetic drug–drug interactions (DDIs) occur when a drug alters the absorption, transport, distribution, metabolism or excretion of a co-administered agent. The occurrence of pharmacokinetic DDIs may result in the increase or the decrease of drug concentrations, which can significantly affect the drug efficacy and safety in patients. Enzyme-mediated DDIs are of primary concern, while the transporter-mediated DDIs are less understood but also important. In this review, we presented an overview of the different mechanisms leading to DDIs, the in vitro experimental tools for capturing the factors affecting DDIs, and in silico methods for quantitative predictions of DDIs. We also emphasized the power and strategy of physiologically based pharmacokinetic (PBPK) models for the assessment of DDIs, which can integrate relevant in vitro data to simulate potential drug interaction in vivo. Lastly, we pointed out the future directions and challenges for the evaluation of pharmacokinetic DDIs.

A short exploration of selected sensitive CYP3A4 substrates (Probe Drug)

2020 ◽  
Vol 14 ◽  
Author(s):  
Sarvesh Sabarathinam ◽  
Thangavel Mahalingam Vijayakumar
Keyword(s):  
Drug Interactions ◽  
Clinical Studies ◽  
In Vivo Studies ◽  
Online Database ◽  
Probe Drug ◽  
Cyp3a4 Substrate ◽  
Cyp3a Inhibitor ◽  
Metabolism Of Xenobiotics ◽  
Pharmacokinetic Drug

Background: CYP450 enzymes in the liver have a significant role in the metabolism of xenobiotics. Probe drug strategy is broadly used to evaluate the pharmacodynamic & pharmacokinetic Drug/ herb-drug interactions/ Fooddrug interactions. Probe drugs guarantee the exact pathway of drug metabolism in the liver by its targeted tractability property. The CYP3A4 isoenzyme metabolizes majority of the drugs (65%). Methods: The characters of targeted probe drugs were observed from admetSAR (version2) online database. Results: Midazolam is widely used as a probe drug because of its peculiar character. Midazolam, affirms the accurate and consistent prediction of pharmacokinetic mediated drug interactions even within nanogram concentrations either within sight of and without a potent CYP3A inhibitor. Remarkably midazolam is used as CYP3A4 substrate in the majority of in vivo studies. Conclusion: However, midazolam shows a good response in all clinical studies because of its lesser half-life and bioavailability when compared with other probe drugs.

scholarly journals Segmental-Dependent Intestinal Drug Permeability: Development and Model Validation of In Silico Predictions Guided by In Vivo Permeability Values

2019 ◽  
Vol 108 (1) ◽  
pp. 316-325 ◽  
Author(s):  
Omri Wolk ◽  
Milica Markovic ◽  
Daniel Porat ◽  
Noa Fine-Shamir ◽  
Moran Zur ◽  
...  
Keyword(s):  
Model Validation ◽  
In Silico ◽  
Drug Permeability ◽  
In Silico Predictions

In Silico Predictions of Drug - Drug Interactions Caused by CYP1A2, 2C9 and 3A4 Inhibition - a Comparative Study of Virtual Screening Performance

2015 ◽  
Vol 34 (6-7) ◽  
pp. 431-457 ◽  
Author(s):  
Teresa Kaserer ◽  
Martina Höferl ◽  
Klara Müller ◽  
Sebastian Elmer ◽  
Markus Ganzera ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Comparative Study ◽  
Drug Interactions ◽  
In Silico ◽  
Screening Performance ◽  
In Silico Predictions ◽  
Virtual Screening Performance
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