Enzyme Induction studies predict a compound’s likelihood to increase clearance of a concomitant (victim) drug by up-regulating (inducing) enzymes that metabolize it. To learn more about this service, visit our Enzyme Induction contract service page.
Enzyme Induction
Webinars
Highlights of the In Vitro Sections of the Draft ICH Drug Interaction Studies Guideline and Comparison with Current Guidance
Presenter: Brian Ogilvie, Ph.D, Vice President of Scientific Consulting at XenoTech In June 2022, the ICH released the first draft of its harmonized Drug Interaction Studies Guideline (M12). The...
Publications
In vitro evaluation suggests fenfluramine and norfenfluramine are unlikely to act as perpetrators of drug interactions
Parthena Martin, Maciej Czerwiński, Pallavi B. Limaye, Brian W. Ogilvie, Steven Smith, Brooks Boyd Abstract Studies support the safety and efficacy of fenfluramine (FFA) as...
Webinars
Filing an IND and Beyond: Development of CTD Section 2.6.4, Pharmacokinetics Written Summary
Presenter: Griff Humphreys, Ph.D, XenoTech Consultant Recorded keynote presentation from XenoTech’s 2022 Seminar Series. Learn about what this important section consists of, the studies that...
Webinars
Role of Sulfotransferases (SULTs) in Drug Metabolism and Potential for Drug-Drug Interactions
Presenter: Maciej Czerwinski, Ph.D., XenoTech Director of Scientific Consulting Abstract: Continuing our series on non-CYP-mediated metabolism pathways, we will be discussing another of the most requested...
Blog
When, Why and How to Conduct CYP2C Induction Studies
Over the years, we have received a lot of questions about cytochrome P450 (CYP) 2C induction studies. In February of...
Webinars
Role of UDP-Glucuronosyltransferases (UGTs) in Drug Metabolism and Drug-Drug Interactions
Presenter: Maciej Czerwinski, Ph.D., XenoTech Director of Scientific Consulting Abstract: The importance of glucuronidation for metabolism of xenobiotics in humans is illustrated by the abundance and...
Blog
ADME/PK & DDI Best Practices Industry Survey Results & Infographic
With over 3500 respondents, only 4% of respondents said they had never experienced any repercussions from postponing these studies...
Webinars
2C or Not 2C: CYP2C Induction Studies for Successful Preclinical Risk Assessment
As a part of IND-enabling preclinical drug development studies companies are required to meet regulatory expectations to evaluate the induction potential of their compound for the cytochrome P450 CYP enzymes CYP1A2, 2B6, 2C8, 2C19 and 3A4. While only CYP1A2, 2B6 and 3A4 must be assessed in the initial induction panel, any observed induction of CYP3A4 requires further investigation of induction potential for enzymes in the CYP2C family due to crosstalk between the PXR and CAR nuclear receptor pathways. This webinar will focus on CYP2C induction and will emphasize when to include CYP2C induction in a study, how to design the study to generate meaningful data and meet the regulatory requirements, what endpoints to measure, and how to interpret results.
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
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
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., 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 will...
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
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?...
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...
Scientific Posters
The evaluation of induction and inhibition potency of various drugs on CYP3A4 and OATP1B1/1B3
Full Title The evaluation of induction and inhibition potency of various drugs on CYP3A4 and OATP1B1/1B3 Authors Ryota Takeuchi, Rena Kusano, Tomoko Sasai, Takami Sarashina,...
Blog
What In Vitro Metabolism and DDI Studies Do I Actually Need?
Though there is no ‘roadmap’ spelling out required studies to achieve regulatory approval for clinical entry, a drug candidate’s metabolism...
Blog
How to Choose the Right Test Systems for Your DMPK Studies
Test systems for DMPK in vitro studies are part of the very foundation of our company. Our labs were borne of...
Blog
Can CYP3A4 Induction Predict P-glycoprotein Induction in DDI Studies?
Generally, a drug’s effects on enzyme and transporter activity are examined independently in a drug development program, but what if...
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...
Webinars
In Vitro Induction Studies: Elements of Design and Important Considerations in Data Analysis
In this webinar, Dr. Joanna Barbara will address frequently asked questions from sponsors seeking induction studies and elaborate on some recommendations we give to achieve successful regulatory submission. Points of discussions will include an overview of enzyme induction studies and critical considerations in design, from determination of supporting data to conclusive interpretation...
Webinars
In Vitro Evaluation of Immunomodulating Drugs as Perpetrators of Drug Interactions
Presenter: Dr. Maciej Czerwinski, XenoTech Director of Consulting; Synopsis: On October 15th, 2018, XenoTech presented on “In Vitro Direct and Cytokine-Mediated Effects of Therapeutic Peptides and other Biologics on CYP Enzymes” at the Peptide ADME Discussion Group Workshop...
Blog
To GLP or not to GLP?
That is the question. . . Knowing the answer may save you time and money Good Laboratory Practices (GLP) are...
Blog
IQ Induction Working Group Publishes Recommendations for Data Interpretation of In Vitro Induction – Focus on CYP3A4 mRNA
XenoTech is proud to have made contributions to the paper entitled, “Considerations from the IQ Induction Working Group in Response...
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...
Blog
UGT Activities, Concomitant Drugs, and DDI
If you have concerns about how your compound may affect UDP-glucuronosyltransferase (UGT) induction and/or inhibition when combined with other therapeutic...
Scientific Posters
The Impact of Various Solvents and Solvent Concentrations on In Vitro Enzyme Induction Assessment
Full Title The Impact of Various Solvents and Solvent Concentrations on In Vitro Enzyme Induction Assessment Abstract Induction of cytochrome P450 (CYP) enzymes is one...
Scientific Posters
Rapid mRNA Induction Screen
Full Title A Rapid High Content Cytochrome P450 (CYP) mRNA Induction Screen for Early Drug Development Abstract Cytochrome P450 (CYP) enzymes play an important role...
Scientific Posters
The Impact of Incomplete Dose-Response Curves on EC50 and Emax Determinations in Enzyme Induction
Full Title The Impact of Incomplete Dose-Response Curves on EC50 and Emax Determinations in Enzyme Induction Assessment Abstract In evaluating the enzyme induction potential of...
Scientific Posters
The Use of Pooled Plated Cryopreserved Human Hepatocytes for the Determination of Metabolic Clearance, CYP Induction, and Uptake Transporter Studies
Full Title The Use of Pooled Plated Cryopreserved Human Hepatocytes for the Determination of Metabolic Clearance, CYP Induction, and Uptake Transporter Studies Abstract During early...
Scientific Posters
Induction of UDP-Glucuronosyltransferases in Cultures of Fresh and Immortalized Human Hepatocytes
Full Title Induction of UDP-Glucuronosyltransferases in Cultures of Fresh and Immortalized Human Hepatocytes Abstract We have examined the induction of UDP-glucuronosyltransferases (UGTs) in primary cultures...
Scientific Posters
Time-course of Cytochrome P450 (CYP450) induction in cultured human hepatocytes
Full Title Time-course of Cytochrome P450 (CYP450) induction in cultured human hepatocytes: Evaluation of activity and mRNA expression profiles for six inducible CYP450 enzymes Abstract...
Publications
An Evaluation of the Dilution Method for Identifying Metabolism-Dependent Inhibitors of Cytochrome P450 Enzymes
Andrew Parkinson, Faraz Kazmi, David B. Buckley, Phyllis Yerino, Brandy L. Paris, Jeff Holsapple, Paul Toren, Steve M. Otradovec and Brian W. Ogilvie Abstract Metabolism-dependent...
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
In situ evaluation of CYP1A2, CYP2B6 and CYP3A4/5 induction in cultured human hepatocytes with a cocktail of probe substrates: A comparison of percent positive control values
Full Title In situ evaluation of CYP1A2, CYP2B6 and CYP3A4/5 induction in cultured human hepatocytes with a cocktail of probe substrates: A comparison of percent...
Scientific Posters
Induction of Liver and Intestinal Cytochrome P450 (CYP) Enzymes in Male and Female Cynomolgus Monkey
Full Title Induction of Liver and Intestinal Cytochrome P450 (CYP) Enzymes in Male and Female Cynomolgus Monkey Abstract The objective of the present study was...
Scientific Posters
Cytochrome P450 3A4 and 1A2 Induction in Immortalized and Primary Cultures of Human Hepatocytes
Full Title Cytochrome P450 3A4 and 1A2 Induction in the Immortalized Hepatocyte Line, Fa2N-4, and Comparison with Primary Cultures of Human Hepatocytes Abstract Primary cultures...
Scientific Posters
The Use of Immortalized Hepatocytes in Induction Studies
Abstract 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...