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Enzyme Inhibition

Enzyme inhibition studies evaluate a compound’s inhibitory effect on drug-metabolizing enzymes to predict the potential for drug-drug interactions that may increase toxicity or reduce therapeutic effect of concomitant medications. To learn more about this service, visit our Enzyme Inhibition contract service page.

 

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...
Publications

In vitro evaluation of fenfluramine and norfenfluramine as victims of drug interactions

Parthena Martin, Maciej Czerwiński, Pallavi B. Limaye, Seema Muranjan, Brian W. Ogilvie, Steven Smith, Brooks Boyd Abstract Fenfluramine (FFA) has potent antiseizure activity in severe,...
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...
Publications

A Guide to In Vitro CYP Inhibition Studies: Elements of Study Design and Important Considerations in Data Analysis

The USFDA, along with other regulatory agencies such as the EMA in Europe and PMDA in Japan, recommend evaluating investigational drugs for their potential to...
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

In Vitro Cholestatic DILI & Mitochondrial Toxicity Studies to Assess Hepatotoxicity

Drug-Induced Liver Injury (DILI) incidents account for more than 10% of all cases of acute liver failure, posing a major clinical and regulatory challenge. While the cause of DILI is multifactorial and difficult to predict, there are known mechanisms...
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., XenoTech Vice President of Scientific Consulting with special guest for Q&A, Lois Haupt, XenoTech Principal Scientist in Program Oversight Many drug candidates...
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...

Webinars

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

Presenter: Jennifer Horkman, Senior Scientist in Program Oversight at 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., 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...

Scientific Posters

An assessment of in vitro inhibition of CYPs, UGTs and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

Full Title An assessment of in vitro inhibition of CYPs, UGTs and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides Presented at the 2019 Marbach Castle Drug-Drug...
Scientific Posters

Inhibitory effect of typical CYP inhibitors under long term incubation in human liver microsomes

Full Title Inhibitory effect of typical CYP inhibitors under long term incubation in human liver microsomes Authors Sho Nishinoaki, Ryo Fujino, Kenta Hashizume, Tsutomu Negama...
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...

Publications

An assessment of the in vitro inhibition of cytochrome P450 enzymes (CYP), UDP-glucuronsyltransferases (UGT) and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

Faraz Kazmi, Phyllis Yerino, Chase McCoy, Andrew Parkinson, David B Buckley and Brian W Ogilvie Oligonucleotides represent an expanding class of pharmacotherapeutics in development for...
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...

Blog

XenoTech Featured on Labiotech.EU

Understand which transporters are involved in a drug’s absorption, distribution & excretion Originally posted on Labiotech.EU How can you build the...

Scientific Posters

In Vitro Evaluation of Ketoconazole and its Alternatives as Non-CYP Inhibitors

Full Title The In Vitro Evaluation of Ketoconazole and its Alternative Clinical CYP3A4/5 Inhibitors (Ritonavir, Clarithromycin and Itraconazole) as Inhibitors of Non-CYP Enzymes Abstract Ketoconazole...
Blog

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

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

Publications

Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure

The world’s oceans are a global reservoir of persistent organic pollutants to which Humans and other animals are exposed. Although it is well known that...
Webinars

Evaluation of Ketoconazole and its Alternative Clinical CYP3A4/5 Inhibitors as Inhibitors of Drug Transporters

Presented by: Lydia Vermeer, Ph.D., Senior Scientist, Drug Transport Ketoconazole is an orally available, synthetic, broad spectrum, antifungal agent. Approved in 1982 by the FDA...
Scientific Posters

Evaluation of Chemical Inhibitors for UDP-glucuronosyltransferase UGT Reaction Phenotyping Assays

Full Title Evaluation of Chemical Inhibitors for UDP-glucuronosyltransferase (UGT) Reaction Phenotyping Assays in Human Liver Microsomes Abstract In the development of a new chemical entity (NCE)...
Scientific Posters

UGT Inhibition Studies in the Presence or Absence of Alamethicin

Full Title UGT Inhibition Studies in the Presence or Absence of Alamethicin: Evaluation of UGT1A1 and UGT2B7 Inhibition in Human Liver Microsomes and Recombinant Enzymes...
Publications

The reliability of estimating Ki values for direct, reversible inhibition of cytochrome P450 enzymes from corresponding IC50 values: A retrospective analysis of 343 experiments

Lois J. Haupt, Faraz Kazmi, Brian W. Ogilvie, David B. Buckley, Brian D. Smith, Sarah Leatherman, Brandy Paris, Oliver Parkinson, and Andrew Parkinson In the...
Publications

Further Characterization of the Metabolism of Desloratadine and its Cytochrome P450 and UDP-Glucuronosyltransferase (UGT) Inhibition Potential: Identification of Desloratadine as a Relatively Selective UGT2B10 Inhibitor

Presented by: Faraz Kazmi, Phyllis Yerino, Joanna E Barbara, and Andrew Parkinson Desloratadine (Clarinex), the major active metabolite of loratadine (Claritin), is a non-sedating antihistamine...
Scientific Posters

Comparison of Ki and IC50 Values for Prototypical Inhibitors of ABC Transporters P-gp and BCRP

Full Title Comparison of Ki and IC50 Values for Prototypical Inhibitors of ABC Transporters P-gp and BCRP Abstract Ki values were determined for prototypical inhibitors...
Scientific Posters

Comparison of Ki and IC50 Values for Prototypical Inhibitors of the Major Drug Uptake Transporters

Full Title Comparison of Ki and IC50 Values for Prototypical Inhibitors of the Major Drug Uptake Transporters Abstract We previously reported on the similarities and...
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

Substrate-Specific Inactivation of CYP3A by the HIV Protease Inhibitors Ritonavir, Saquinavir and Amprenavir

Full Title Substrate-Specific Inactivation of CYP3A by the HIV Protease Inhibitors Ritonavir, Saquinavir and Amprenavir Abstract HIV protease inhibitors (PIs), such as ritonavir, saquinavir, and...
Publications

Metabolism-Dependent Inhibition of CYP3A4 by Lapatinib: Evidence for Formation of a Metabolic Intermediate Complex with a Nitroso/Oxime Metabolite Formed via a Nitrone Intermediate

Barbara JE, Kazmi F, Parkinson A, Buckley DB Metabolism-dependent inhibition (MDI) of cytochrome P450 (P450) enzymes has the potential to cause clinically relevant drug-drug interactions....
Webinars

Exploring the Mechanism of CYP3A4 Inactivation by Lapatinib Through In Vitro Metabolite Char.

Presented by: Joanna Barbara, Ph.D. Metabolism-dependent inhibition of cytochrome P450 enzymes has the potential to cause clinically-relevant drug-drug interactions. Alkylamine drugs are known for their propensity...
Publications

Use of enzyme inhibitors to evaluate the conversion pathways of ester and amide prodrugs: A case study example with the prodrug ceftobiprole medocaril

Gary Eichenbaum, Jennifer Skibbe, Andrew Parkinson, Mark D. Johnson, Dawn Baumgardner, Brian Ogilvie, Etsuko Usuki, Fred Tonelli, Jeff Holsapple and Anne Schmitt-Hoffmann An approach was...
Scientific Posters

Esomeprazole, omeprazole sulfone, 5-O-desmethyl omeprazole and 5-hydroxylansoprazole are in vitro metabolism-dependent inhibitors of CYP2C19

Full Title Esomeprazole, omeprazole sulfone, 5-O-desmethyl omeprazole and 5-hydroxylansoprazole are in vitro metabolism-dependent inhibitors of CYP2C19 Abstract The intensively researched interaction between clopidogrel and proton...
Scientific Posters

Can Ki values for direct inhibition of CYP enzymes be reliably estimated from IC50 values?

Full Title Can Ki values for direct inhibition of CYP enzymes be reliably estimated from IC50 values? Abstract Regulatory agencies recommend that the potential for...
Scientific Posters

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

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

Full Title Identification of a novel carbamoyl glucuronide as a metabolism-dependent inhibitior of CYP2C8 Abstract Glucuronidation is a major route of drug biotransformation and detoxification,...
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

Full Title 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...