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Drug Drug Interactions (DDI)

Drug-drug interactions (DDI) can be fatal or harmful to a patient taking multiple medications by causing up-regulation or inhibition of drug-metabolizing enzymes or altering activity of drug transporters. Understanding DDI potential of an investigational new drug before clinical trials can help bolster safety data and evaluate risk. To learn more about why DDI potential of a compound is important or to contract relevant studies, visit our Drug-Drug Interactions (DDI) informational page.

 

Webinars

ADME 101: Model-Based Approaches to DDI Risk Prediction – Navigating the Transition from In Vitro Data to In Silico Modeling

This informative ADME 101 discusses In Vitro to In Vivo Extrapolation (IVIVE) and how a model-based approach following routine perpetrator potential studies (i.e. CYP inhibition, CYP induction, and transporter inhibition) assessing clinical potential may eliminate the need of conducting clinical studies. Listen in as Dr. Limaye outlines a step–wise approach for bringing robustness to the prediction, including...
Webinars

Suicide by Binding: Putting Time-Dependent Inhibition of CYP Enzymes into Perspective

Presenter: Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting with special guest for Q&A, Lois Haupt, SEKISUI XenoTech Principal Scientist in Program Oversight Many...
Regulatory Documents

2020 FDA Draft Guidance, “Drug-Drug Interaction Assessment for Therapeutic Proteins Guidance for Industry”

In August 2020, the FDA released the draft guidance for industry to evaluate therapeutic proteins for drug-drug interaction (DDI) potential using a risk-based approach.  ...
Webinars

ADME 101: Enzyme Induction Studies

The clearance of a drug can be increased and its effectiveness or safety compromised if it is co-administered with a second drug that induces the enzyme responsible...
Blog

Drug-Drug Interaction (DDI) Prediction Models Following In Vitro Studies in Preclinical Development

In preclinical development, a drug will be evaluated for potential to cause a drug-drug interaction (DDI) using in vitro experiments and then calculations that...

Blog

Important DDI Considerations for Repurposing Drugs to Treat COVID-19

“Given the rapid spread of COVID-19 and its relatively high mortality, filling the gap for coronavirus-specific drugs is urgent. […]...

Blog

What is DMPK and how does it fit into drug development?

Drug metabolism and pharmacokinetics (DMPK) is a core discipline in drug development that considers the biotransformation of a drug compound...

Webinars

In Vitro Inhibition Studies: Elements of Design and Important Considerations in Data Analysis

Presenter: Jennifer Horkman, Senior Scientist in Program Oversight at SEKISUI XenoTech When evaluating drug-drug interaction (DDI) risk of an investigational drug, a battery of studies is needed to investigate victim/perpetrator...
Blog

ADME and Drug-Drug Interactions for the Toxicologist

Highlights from the recent webinar presented by our newest expert consultant, Dr. Pallavi Limaye In her recent webinar (now available for...

Webinars

Comparison Between the Final US FDA, Japan PMDA, and EMA In Vitro DDI Guidance Documents: Are We Finally Harmonized?

Presenter: Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting In January, the FDA published its final guidance for industry on in vitro drug-drug interaction (DDI) studies. Dr. Ogilvie...
Webinars

In Vitro ADME & Drug-Drug Interaction Considerations for Toxicologists

Presenter: Pallavi Limaye, Ph.D., DABT, SEKISUI XenoTech Director of Scientific Consulting with special Q&A guest, Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting Originally scheduled to...
Webinars

The Basics of In Vitro Xenobiotic Metabolism and Drug-Drug Interaction Investigations: Applicability to All Xenobiotics

Since SOT’s 59th Annual Meeting and ToxExpo has been canceled due to COVID-19 concerns, we are bringing the tradeshow to you! SOT is hosting this...
Blog

COVID-19 Updates

As a global Life Sciences and Healthcare company, SEKISUI XenoTech recognizes the seriousness of the Coronavirus Pandemic. We are constantly...

Blog

In Vitro Evaluation of Drug-Drug Interaction (DDI) Potential

In its most recent in vitro drug interaction guidance update, the US Food and Drug Administration (FDA) emphasized harmony with the...

Blog

Four ways to optimize preclinical in vitro data to mitigate risk of late-stage clinical failure

1. Collect high-quality data to make informed, confident go/no go decisions for moving your drug candidate forward If you need...

Scientific Posters

Comparison Between the Final US FDA, Japan PMDA and EMA In Vitro DDI Guidance

Comparison Between the Final US FDA (2020), the Final Japan PMDA (2018), and Final EMA (2013) In Vitro DDI Guidance Documents: Are We Finally Harmonized?...
Webinars

ADME 101: Metabolite ID & Characterization Studies FAQ

Presenter: Mark Horrigan, SEKISUI XenoTech Principal Scientist, Program Oversight In this short, information-packed ADME 101 video, one of our study directors discusses the main frequently asked...
Blog

Timing of In Vitro Studies: Early, Thorough ADME for Your Compound’s Success

Beyond the need for evidence that a drug works, Food and Drug Administration (FDA) and other regulatory bodies around the...

Publications

Effects of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and interferon-α2a on P450 enzymes in human hepatocytes in vitro

Maciej Czerwiński, Krystal Gilligan, Kevin Westland, Brian W. Ogilvie Some immunomodulatory agents stimulate the release of cytokines capable of suppressing P450 enzymes and potentially affecting pharmacokinetics of coadministered medications. Cytokines...
Webinars

Are in vitro metabolism and DDI studies critical for an IND?

Presenter: Greg Loewen, Director of Technical Support at SEKISUI XenoTech Continuing our ADME 101 presentation series assisting researchers and industry professionals with navigating ADME, DMPK, and...
Blog

In Vitro Induction Studies: Elements of Design and Important Considerations in Data Analysis

Why do induction studies? Induction potential is an important piece of the drug-drug interaction (DDI) component of an IND submission. Simply put, we...

Blog

Minding Your Binding: Plasma Protein Binding Potential Study Now Available at Our US and Japan Labs

While liver and intestine are important in ADME, behavior in blood is also crucial. When an orally administered drug or...

Webinars

In Vitro Evaluation of Immunomodulating Drugs as Perpetrators of Drug Interactions

Presenter: Dr. Maciej Czerwinski, SEKISUI XenoTech Director of Consulting Synopsis: On October 15th, 2018, SEKISUI XenoTech presented on “In Vitro Direct and Cytokine-Mediated Effects of Therapeutic Peptides...
Blog

Important Considerations for the Conduct of In Vitro Drug Transporter Assays

Not only can drug transporters affect the absorption and excretion of drugs, they can be involved in pharmacokinetic-based drug-drug interactions...

Publications

2017 FDA Guidance: Many In Vitro DDI Evaluations Should Precede FIH Studies

Dr. Brian Ogilvie, Andrea Wolff While the 2017 FDA DDI guidance contains many important changes, the earlier timing of drug-drug interaction studies is perhaps the most...
Publications

Chapter 6: Biotransformation of Xenobiotics

Andrew Parkinson, Brian W. Ogilvie, David B. Buckley, Faraz Kazmi and Oliver Parkinson This book chapter will be part of Casarett and Doull’s Toxicology: The...
Publications

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies

Jane R Kenny, Diane Ramsden, David B Buckley, Shannon Dallas, Conrad Fung, Michael Mohutsky, Heidi J Einolf, Liangfu Chen, Joshua G Dekeyser, Maria Fitzgerald, Theunis...
Scientific Posters

Current In Vitro DDI Regulatory Guidance (Reference Poster)

Brian W. Ogilvie1 and Andrew Parkinson2 1SEKISUI XenoTech, LLC, Kansas City, KS, USA and 2XPD Consulting, Shawnee, KS, USA Abstract: In September, 2017, the Japan PMDA revised its...
Blog

In Vitro DDI Regulatory Guidance Reference Poster

At the 2018 Marbach Castle Drug-Drug Interaction Workshop in Germany, Dr. Brian Ogilvie, Vice President of Scientific Consulting, presented a comparison...

Publications

Direct and cytokine‐mediated effects of albumin‐fused growth hormone, TV‐1106, on CYP enzyme expression in human hepatocytes in vitro

Maciej Czerwiński, Immaculate Amunom, Victor Piryatinsky, Hussein Hallak, Yousif Sahly, Oren Bar‐Ilan, Paul Bolliger, Merav Bassan Some biologics can modulate cytokines that may lead to...
Webinars

Comparison Between the US FDA, EU EMA and Japan PMDA In Vitro DDI Guidance Documents: Are We Close to Harmonization?

Hear more about updates in regulatory expectations for drug metabolism and DDI data between FDA, EMA, and PMDA
Webinars

Essential Considerations on the New FDA In Vitro DDI Guidance (the What, the Why, and the Wow)

Presenter: Brian Ogilvie, Ph.D., SEKISUI XenoTech Vice President of Scientific Consulting In October, the FDA revised and split its 2012 draft guidance for industry on in vitro drug-drug...
Blog

Further Research on the Drug-Drug Interaction Between Gemfibrozil and Repaglinide Presented

The clinically-relevant drug-drug interaction (DDI) between the dyslipidemia drug gemfibrozil and the antidiabetic repaglinide is well-documented throughout the literature. In...

Scientific Posters

Further exploration into the DDI between Gemfibrozil & Repaglinide in rats

Presented by: Chase I. McCoy, Forrest A. Stanley, Chandra Kollu, Seema Muranjan, Krystal M. Green and Joanna E. Barbara Abstract The clinically-relevant drug-drug interaction (DDI)...
Blog

Considerations In Response to Drug-Drug Interaction Guidances

Check out the recent IQ consortium publication: Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from...

Publications

DDI Guidance Recommendations on Down-Regulation, CYP2C Induction and CYP2B6 Control

Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on Down-regulation, CYP2C Induction and CYP2B6 Positive Control...
Webinars

Drug Metabolizing Enzymes and Transporters in NASH

Research Application of Variants of Fatty Liver Disease (FLD) Tissues Presented by Maciej Czerwinski, Ph.D., SEKISUI XenoTech Director of Consulting SEKISUI XenoTech is committed to the support...
Webinars

Adverse drug interaction risks in genetically-definied

Presenter:  Maciej Czerwinski, Ph.D., Director of SEKISUI XenoTech Products R&D Synopsis: An increased appreciation of the effects of genetic variability on the pharmacokinetic and pharmacodynamic properties of xenobiotics creates a...
Blog

XenoTech Scientists Publish Paper, Present Research Evaluating Ketoconazole and its Alternative Clinical CYP3A4-5 Inhibitors as Inhibitors of Drug Transporters

SEKISUI XenoTech scientists published a paper in Drug Metabolism and Disposition evaluating Ketoconazole and its alternative clinical CYP3A4-5 inhibitors as inhibitors of drug...

Scientific Posters

In Vitro Assessment of the Drug-Drug Interaction of Rasagiline and Its Metabolite Aminoindan

In Vitro Assessment of the Pharmacokinetic Drug-Drug Interaction Potential of Rasagiline and Its Major Metabolite Aminoindan Rasagiline mesylate (PAI) is the active pharmaceutical ingredient of...
Scientific Posters

Exploring the Drug-Drug Interaction Between Gemfibrozil and Repaglinide in Rats

Exploring the Drug-Drug Interaction Between Gemfibrozil and Repaglinide in Rats: Metabolism and Transport A clinically-relevant drug-drug interaction (DDI) between the dyslipidemia drug gemfibrozil and the antidiabetic...
Publications

Anti-CD28 Monoclonal Antibody-stimulated Cytokines Released from Blood Suppress CYP1A2, CYP2B6 and CYP3A4 in Human Hepatocytes In Vitro

Maciej Czerwiński, Faraz Kazmi, Andrew Parkinson, and David B. Buckley Like most infections and certain inflammatory diseases, some therapeutic proteins cause a cytokine-mediated suppression of...
Publications

In vitro inhibition of human liver cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes by rose bengal: system-dependent effects on inhibitory potential

Faraz Kazmi, Lois J. Haupt, Jennifer R. Horkman, Brian D. Smith, David B. Buckley, Eric A. Wachter, and Jamie M. Singer 1. Rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein)...
Scientific Posters

An in vitro test system to evaluate drug-drug interactions with biologics

Inflammation, infection, vaccination, and some marketed therapeutic proteins (biologics) are associated with cytokine-mediated suppression (down-regulation) of drug-metabolizing enzymes (DME). Biologics, such as monoclonal antibodies, can trigger...
Scientific Posters

Evaluation of dilution, dialysis and ultracentrifugation methods to assess the reversibility of metabolism-dependent inhibitors (MDIs) of cytochrome P450 (CYP) enzymes

Evaluation of dilution, dialysis and ultracentrifugation methods to assess the reversibility of metabolism-dependent inhibitors (MDIs) of cytochrome P450 (CYP) enzymes Metabolism-dependent inhibition (MDI) of P450...
Publications

The Proton Pump Inhibitor, Omeprazole, but Not Lansoprazole or Pantoprazole, Is a Metabolism-Dependent Inhibitor of CYP2C19: Implications for Coadministration with Clopidogrel

Ogilvie BW, Yerino P, Kazmi F, Buckley DB, Rostami-Hodjegan A, Paris BL, Toren P, Parkinson A As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole...
Scientific Posters

In vitro inhibition and induction of human liver cytochrome P450 enzymes by NTBC and its metabolism in human liver microsomes

In vitro inhibition and induction ofHuman liver cytochrome P450 enzymes by NTBC and its metabolism in human liver microsomes 2-(2-Nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC, also known as...
Scientific Posters

Identification of a novel carbamoyl glucuronide as a metabolism-dependent inhibitior of CYP2C8

Glucuronidation is a major route of drug biotransformation and detoxification, whereby a drug is conjugated with glucuronic acid in a reaction catalyzed by UDP glucuronosyltransferases...
Scientific Posters

Pitfalls in the Design of Metabolism-Dependent CYP Inhibition (MDI) Experiments With a Dilution Step: Inhibitor Depletion by Metabolism and/or Microsomal Binding Leads to Underestimation of the Shifted IC50 Value

We previously demonstrated that, when a dilution step is used to assess MDI potential (i.e., IC50 shift experiments), IC50 values for direct-inhibition and MDI should...
Scientific Posters

Induction of Liver and Intestinal Cytochrome P450 (CYP) Enzymes in Male and Female Cynomolgus Monkey

Abstract The objective of the present study was to determine the effects of various prototypical inducers on the activity and mRNA expression of multiple CYP...
Scientific Posters

Cytochrome P450 3A4 and 1A2 Induction in Immortalized and Primary Cultures of Human Hepatocytes

Cytochrome P450 3A4 and 1A2 Induction in the Immortalized Hepatocyte Line, Fa2N-4, and Comparison with Primary Cultures ofHuman Hepatocytes Abstract Primary cultures ofHuman hepatocytes are...
Scientific Posters

The Use of Immortalized Hepatocytes in Induction Studies

Introduction Primary cultures of human hepatocytes are widely used to evaluate the cytochrome P450 (CYP) enzyme-inducing potential and/or toxicity of drug candidates. However, the availability...
Publications

Chapter 7: In Vitro Approaches for Studying the Inhibition of Drug-Metabolizing Enzymes and Identify

Thank you for your interest in SEKISUI XenoTech’s last edition of… Chapter 7: In Vitro Approaches for Studying the Inhibition of Drug-Metabolizing Enzymes and Identifying...

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