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Drug Metabolism

Drug metabolism studies profile metabolic pathways and likely metabolites formed by a compound, as well as identify drug-metabolizing enzymes involved in its biotransformation. For more information about these services, visit our Drug Metabolism contract studies page.

 

Webinars

ADME 101: Reaction Phenotyping Studies in Drug Metabolism

Presenter: Andrew Taylor, Ph.D., Services Technical Support Manager It is important to identify the enzymes that significantly contribute to the metabolism of a drug candidate...
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...

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...
Blog

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

The main aim of drug development is to get a compound that has a therapeutic effect into the form of...

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

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...

Blog

How can in vitro and in vivo studies help me understand my drug’s clearance?

Systemic clearance, denoting how much drug is cleared from a volume of blood per unit of time, is of critical...

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...

Blog

How Can I Make Sure My Data Meets Regulatory Expectations?

Regulatory authorities publish updated guidance documents that share their expectations for endpoints and test systems with drug developers, but sometimes it is difficult to...

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...
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...

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...
Webinars

ADME 101: DMPK and ADME in Drug Development

Presenter: Joanna Barbara, Ph.D., Vice President of Scientific Operations at SEKISUI XenoTech We are pleased to present SEKISUI XenoTech’s first ADME 101 series webinar, Acronyms Abound:...
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...

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

Strategies to improve the predictions accuracy of hepatic intrinsic clearance of three antidiabetic drugs: application of the extended clearance concept and consideration of the effect of albumin on CYP2C metabolism and OAT1B1-mediated hepatic uptake

Ryo Fujino, Kenta Hashizume, Shinsuke Aoyama, Kazuya Maeda, Kiyomi Ito, Kota Toshimoto, Wooin Lee, Shin-ichi Ninomiya, Yuichi Sugiyama The antidiabetic drugs glibenclamide, repaglinide, and nateglinide...
Scientific Posters

Microsomal cytochrome P450 (CYP) enzyme activities in nonalcoholic steatohepatitis (NASH) livers

Maciej Czerwinski1, Brian Oberheide1, Nicholas Hatfield1, Bill Ewy1, Christopher Seib1, Eva Gatineau2, Frederique Yiannikouris2, Brian Ogilvie1 1 SEKISUI XenoTech, LLC 2 University of Kentucky, Department...
Blog

NADPH RapidStart Regeneration System for Extended Metabolism

Originally published in tebu-bio’s Being Bioreactive. To purchase SEKISUI XenoTech’s products in the EU, please visit tebu-bio’s website. NADPH is a critical...

Blog

Maximize Metabolic Activities by Limiting Hepatocyte Cryoinjury

Cryopreservation and thawing of primary hepatocytes causes inherent damage to the cells. Traditional pooling methods require cells to undergo two separate cryopreservation...

Publications

Direct and cytokine‐mediated effects of albumin‐fused growth hormone on CYP expression

Some biologics can modulate cytokines that may lead to changes in expression of drug‐metabolizing enzymes and cause drug‐drug interactions (DDI). DDI potential of TV‐1106—an albumin‐fused growth...
Blog

Recombinant CYP Bactosomes: Versatile Formats for Many ADME Applications

Originally published in tebu-bio’s Being Bioreactive. To purchase recombinant CYPs in the EU, please visit tebu-bio’s website. For North American orders, please follow...

Blog

What To Do with Microsome Stable Low Turnover Compounds

Compounds that exhibit high metabolic stability in hepatocytes and subcellular fractions (S9, microsomes and cytosol) can be a challenge for ADME scientists. These in...

Scientific Posters

Evaluation of interspecies metabolic activities for Non-CYP enzymes, suitable incubation conditions

Recently, lead compound screenings has become widely used in drug development. This has led to the development of increasing range of lead compound structures with...
Blog

Hepatosure Hepatocytes: The Largest Donor Pool For Your DMPK Applications

Pooled human hepatocytes can complement a selection of hepatocytes from various species for metabolite profiling, species comparison and evaluation of potential human-specific metabolites. HepatoSure® is the...

Blog

Cold Storage Solution Linked to Lower AO, XO Activity

At the time of organ recovery, human livers that have been donated for research are flushed with an ice-cold perfusion...

Blog

Considerations When Studying Esterase Activities in the Intestine

The gastrointestinal wall is a significant site of first-pass metabolism for oral drugs, which is commonly associated with CYP450 and...

Scientific Posters

Effects of organ preservation solution on aldehyde oxidase and xanthine oxidase activity in pooled human liver S9

Non-transplant quality human livers donated for research are a common source of both cellular and subcellular material utilized in in vitro drug metabolism studies. At...
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...
Scientific Posters

Evaluation of the CYP metabolic activities in the presence of albumin in human liver microsomes

Cytochrome P450 (CYP) isoforms are responsible for the metabolism of the majority of drugs in human. An intrinsic clearance (CLint) determined from in vitro intrinsic...
Scientific Posters

In vitro characterization of human liver lysosomes isolated from fresh tissue

Evaluation of lysosomal catabolism is an integral part of the development of biologic drugs including antibody-drug conjugates (ADC). Biologics can enter the cell by fluid-phase...
Scientific Posters

Efficient use of chimeric mice with humanized livers for drug development support

Chimeric mice withHumanized livers can be used to obtain supportive data for selecting the best candidate compound for new drug development. To utilize this costly...
Scientific Posters

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

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

Comparative Investigation of Benzoapyrene, Procaine and Nevirapine Metabolism in Human Hepatocytes

A Comparative Investigation of Benzo[a]pyrene, Procaine and Nevirapine Metabolism inHuman Hepatocytes and a 3D Skin Tissue Model Skin metabolism is an important contributor to the...
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

Effects of Albumin-Fused Human Growth Hormone TV-1106 on CYP Enzyme Expression in Human Hepatocytes

Direct and Cytokine-Mediated Effects of Albumin-FusedHuman Growth Hormone, TV-1106, on CYP Enzyme Expression in Human Hepatocytes In Vitro Drug-drug interactions involving therapeutic proteins that can...
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

Automated Plasma Protein Binding Using Rapid Equilibrium Dialysis

High Content Automated Plasma Protein Binding Screening and Definitive Assays Using Rapid Equilibrium Dialysis for Drug Development A pharmacokinetic/pharmacodynamic principle important in drug development is...
Publications

A long-standing mystery solved: The formation of 3-hydroxydesloratadine is catalyzed by CYP2C8 but prior glucuronidation of desloratadine by UGT2B10 is an obligatory requirement

Faraz Kazmi, Joanna E. Barbara, Phyllis Yerino and Andrew Parkinson Desloratadine (Clarinex®), the major active metabolite of loratadine (Claritin®), is a non-sedating long-lasting antihistamine widely used for...
Scientific Posters

Assessment Under Initial Rate Conditions

Assessment Under Initial Rate Conditions of the Selectivity and Time Course of Cytochrome P450 Inactivation in PooledHuman Liver Microsomes and Hepatocytes: Optimization of Inhibitor Conditions...
Scientific Posters

Comparison of XenoTech Hepatocytes to HepaRG® Cell Line

Determination of Low Intrinsic Clearance Values using PrimaryHuman Hepatocytes and the HepaRG® Cell Line – A Comparison of Methods Svanberg, et al – AstraZeneca R&D...
Scientific Posters

SLAS 2014 – Automated Metabolic Stability

High content automated metabolic stability and CYP inhibition cocktail screening assays for early drug development. The assessment of metabolic stability and cytochrome P450 (CYP) inhibition...
Scientific Posters

ISSX 2013 – Repaglinide Case Study

High-resolution mass spectrometry for rapid metabolite characterization and reaction phenotyping: a case study with repaglinide  Assessing the involvement of specific cytochrome P450 (P450) enzymes in...
Scientific Posters

ISSX 2013 – Midazolam Clearance

Midazolam clearance in human hepatocytes is restricted compared with human liver microsomes but not by cell permeability or cofactor availability In our previous work (see...
Scientific Posters

ISSX 2013 – Clearance of CYP2D6 and CYP3A4

Test system-dependent clearance of CYP2D6 and CYP3A4/5 substrates: A comparison of human liver microsomes and cryopreservedHuman hepatocytes The in vitro to in vivo extrapolation (IVIVE)...
Scientific Posters

ISSX 2013 – Aldehyde Oxidase

Selection of human liver S9 and cytosol fractions for evaluating clearance by aldehyde oxidase (AO): The impact of low versus high AO activity lots. Aldehyde oxidase (AO) is a...
Webinars

Aldehyde Oxidase: Why In Vitro Absolute Activity Doesn’t Matter

Presented by: Brian Ogilvie and Faraz Kazmi Biotransformation by aldehyde oxidase (AO) is an important clearance mechanism for many drugs and drug candidates, with increasing...
Publications

Exploring the Utility of High-Resolution MS with Post-Acquisition Data Mining for Simultaneous Exogenous and Endogenous Metabolite Profiling

Exploring the Utility of High-Resolution MS with Post-Acquisition Data Mining for Simultaneous Exogenous and Endogenous Metabolite Profiling Presented by: Barbara JE, Buckley DB, Horrigan MJ...
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....
Publications

Lysosomal Sequestration (Trapping) of Lipophilic Amine (Cationic Amphiphilic) Drugs in Immortalized Human Hepatocytes (Fa2N-4 cells)

Kazmi F, Hensley T, Pope C, Funk RS, Loewen GJ, Buckley DB, Parkinson A Lipophilic (logP > 1) and amphiphilic drugs (also known as cationic...
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

High-Resolution Mass Spectrometry Elucidates Metabonate (False Metabolite) Formation from Alkylamine Drugs During In Vitro Metabolite Profiling

Presented by: Barbara JE, Kazmi F, Muranjan S, Toren PC, Parkinson A In vitro metabolite profiling and characterization experiments are widely employed in early drug...
Publications

Catechol and aldehyde moieties of 3,4-dihydroxyphenylacetaldehyde contribute to tyrosine hydroxylase inhibition and neurotoxicity

Lydia M. Vermeer , Virginia R. Florang , Jonathan A. Doorn Parkinson’s disease (PD) is a progressive neurodegenerative disorder which leads to the selective loss...
Publications

Activator Protein-1 Regulation of Murine Aldehyde Dehydrogenase 1a1

Previously we demonstrated that aldehyde dehydrogenase (ALDH) 1a1 is the major ALDH expressed in mouse liver and is an effective catalyst in metabolism of lipid aldehydes...
Scientific Posters

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

Esomeprazole, omeprazole sulfone, 5-O-desmethyl omeprazole and 5-hydroxylansoprazole are in vitro metabolism-dependent inhibitors of CYP2C19 The intensively researched interaction between clopidogrel and proton pump inhibitors (PPIs) and the...
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...
Publications

Comprehensive Quantitative and Qualitative Liquid Chromatography–Radioisotope–Mass Spectrometry Analysis for Safety Testing of Tolbutamide Metabolites Without Standard Samples

Zenzaburo Tozuka, Shinsuke Aoyama, Kohei Nozawa, Shoji Akita, Toshinari Oh-Hara, Yasuhisa Adachi, Shin-Ichi Ninomiya ADME & Tox. Research Institute, SEKISUI Medical Company, Ltd., Tokai, Ibaraki...
Scientific Posters

The effect of multiple cryopreservation cycles on drug-metabolizing enzymes in human hepatocytes

Cryopreserved hepatocytes provide a convenient in vitro test system to study the phase-1 and phase-2 metabolism of new chemical entities; however cryopreservation (freeze-thaw cycles) can...
Scientific Posters

Accurate mass spectrometry elucidates a misleading metabonate formed from amine-containing drugs in reactive metabolite screening assays

Accurate mass spectrometry elucidates a misleading metabonate formed from amine-containing drugs in reactive metabolite screening assays The propensity of drug candidates to undergo cytochrome P450...
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

The effect of multiple cryopreservation cycles on drug-metabolizing enzymes in human hepatocytes

The effect of multiple cryopreservation cycles on drug-metabolizing enzymes inHuman hepatocytes Cryopreserved hepatocytes provide a convenient in vitro test system to study the phase-1 and...
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

Effects of Gender, Age and Ethnicity on Human Cytochrome P450 Activity

Introduction It has been well documented that the expression of CYP enzymes is influenced by endogenous factors, such as genetic polymorphisms and hormone levels, and...
Scientific Posters

Microsomes and S9 Prepared from Renal Tissue Yield High CYP, FMO and UGT Activities that are Stable…

Microsomes and S9 Prepared from Renal Tissue Yield High CYP, FMO and UGT Activities that are Stable over Multiple Freeze/Thaw Cycles Abstract We have developed...
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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