Combining stem cell-derived hepatocytes with impedance sensing to better predict human drug toxicity.

Abstract:

:Background: The liver plays a central role in human drug metabolism. To model drug metabolism, the major cell type of the liver, the hepatocyte, is commonly used. Hepatocytes can be derived from human and animal sources, including pluripotent stem cells. Cell-based models have shown promise in modeling human drug exposure. The assays used in those studies are normally 'snap-shot' in nature, and do not provide the complete picture of human drug exposure. Research design and methods: In this study, we employ stem cell-derived hepatocytes and impedance sensing to model human drug toxicity. This impedance-based stem cell assay reports hepatotoxicity in real time after treatment with compounds provided by industry. Results: Using electric cell-substrate impedance Sensing (ECIS), we were able to accurately measure drug toxicity post-drug exposure in real time and more quickly than gold standard biochemical assays. Conclusions: ECIS is robust and non-destructive methodology capable of monitoring human drug exposure with superior performance to current gold standard 'snapshot' assays. We believe that the methodology presented within this article could prove valuable in the quest to better predict off-target effects of drugs in humans.

authors

Zhou W,Graham K,Lucendo-Villarin B,Flint O,Hay DC,Bagnaninchi P

doi

10.1080/17425255.2019.1558208

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

77-83

issue

1

eissn

1742-5255

issn

1744-7607

journal_volume

15

pub_type

杂志文章
  • Evaluation of lorcaserin for the treatment of obesity.

    abstract:INTRODUCTION:Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.798643

    authors: Berlie HD,Hurren KM

    更新日期:2013-08-01 00:00:00

  • Coffee in cancer chemoprevention: an updated review.

    abstract:INTRODUCTION:Chemoprevention of cancer refers to the use of natural or synthetic compounds to abolish or perturb a variety of steps in tumor initiation, promotion, and progression. This can be realized through different mechanisms, including activation of free radical scavenging enzymes, control of chronic inflammation...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1080/17425255.2021.1839412

    authors: Ismail T,Donati-Zeppa S,Akhtar S,Turrini E,Layla A,Sestili P,Fimognari C

    更新日期:2021-01-01 00:00:00

  • Pharmacokinetic evaluation of pregabalin for the treatment of generalized anxiety disorder.

    abstract:INTRODUCTION:Pregabalin is an alternative compound to SSRIs and SNRIs for the first-line treatment of generalized anxiety disorder (GAD). Areas covered: We describe the pharmacokinetic properties of pregabalin and their implications for the treatment of GAD. A search in the main database sources (Medline, ISI, Web of K...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1281247

    authors: Buoli M,Caldiroli A,Serati M

    更新日期:2017-03-01 00:00:00

  • In silico models for genotoxicity and drug regulation.

    abstract:INTRODUCTION:Whereas in the past, (Q)SAR methods have been largely used to support the design of new drugs, in the last few decades, there has been a new interest in its applications for the assessment of drug safety. In particular, the ICH M7 guideline has introduced the concept that (Q)SAR predictions for the Ames mu...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1080/17425255.2020.1785428

    authors: Benigni R,Bassan A,Pavan M

    更新日期:2020-08-01 00:00:00

  • Highlights of the XII International Congress on Toxicology, 19 - 23 July 2010, Barcelona, Spain.

    abstract:IMPORTANCE OF THE FIELD:There are few true international meetings dedicated to covering multiple areas of toxicology. The XII International Congress of Toxicology (IUTOX) held from 19 to 23 July 2010 in Barcelona, Spain is one such meeting. The IUTOX is important as its emphasis is on chemical safety and integrating ap...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1517/17425255.2010.521152

    authors: Anadón A,Valerio LG Jr

    更新日期:2010-11-01 00:00:00

  • Zebrafish for drug toxicity screening: bridging the in vitro cell-based models and in vivo mammalian models.

    abstract:INTRODUCTION:Over the past decade, zebrafish have been tasked to play important roles from modeling human diseases to finding cures for them. Inadvertently, these fish now find themselves swimming along the drug development pipeline. A number of studies have been conducted to see if these small fish are up to the task ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.562197

    authors: Sukardi H,Chng HT,Chan EC,Gong Z,Lam SH

    更新日期:2011-05-01 00:00:00

  • Cinacalcet: pharmacological and clinical aspects.

    abstract::The calcium sensing receptor (CaSR) is expressed in cells secreting calcium-regulating hormones, in cells involved in calcium transport and in many other tissues, with an as yet not completely defined role. In parathyroid cells, the CaSR stimulation inhibits parathyroid hormone (PTH) secretion, synthesis and parathyro...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425250802587017

    authors: Messa P,Alfieri C,Brezzi B

    更新日期:2008-12-01 00:00:00

  • Efavirenz in the therapy of HIV infection.

    abstract:IMPORTANCE OF THE FIELD:The use of the first generation non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) as a component of first-line antiretroviral therapy has been accepted worldwide. EFV is the only antiretroviral agent currently on the market that has been combined with emtricitabine and tenofovir dis...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425250903483207

    authors: Rakhmanina NY,van den Anker JN

    更新日期:2010-01-01 00:00:00

  • Pharmacokinetic drug evaluation of mepolizumab for the treatment of severe asthma associated with persistent eosinophilic inflammation in adults.

    abstract:INTRODUCTION:Mepolizumab is a humanized monoclonal antibody that binds to and inactivates IL-5. It is available as a subcutaneous preparation. The practical application of mepolizumab is as an add-on therapy in the treatment of severe eosinophilic asthma. Areas covered: This article was created from a comprehensive lit...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1406919

    authors: Kallur L,Gonzalez-Estrada A,Eidelman F,Dimov V

    更新日期:2017-12-01 00:00:00

  • Evaluation of sofosbuvir, velpatasvir plus voxilaprevir as fixed-dose co-formulation for treating hepatitis C.

    abstract:INTRODUCTION:The fixed-dose combination of three direct-acting antivirals (DAA), namely sofosbuvir, velpatasvir and voxilaprevir is the first pangenotypic, single tablet regimen developed for the treatment of HCV infection. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy and safety of the co-formulation...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1359254

    authors: Soriano V,Benítez-Gutiérrez L,Arias A,Carrasco I,Barreiro P,Peña JM,de Mendoza C

    更新日期:2017-09-01 00:00:00

  • Green tea extract and the risk of drug-induced liver injury.

    abstract:INTRODUCTION:Catechins of green tea extract (GTE) have been associated with the rare risk of hepatotoxicity in a few individuals. As GTE were coadministered with synthetic drugs in some hepatotoxicity cases, uncertainty emerged whether GTE are a risk factor of drug-induced liver injury (DILI). AREAS COVERED:Case repor...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2014.971011

    authors: Teschke R,Zhang L,Melzer L,Schulze J,Eickhoff A

    更新日期:2014-12-01 00:00:00

  • Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes.

    abstract:INTRODUCTION:The review aims to discuss effects of vitrectomy on pharmacokinetics of anti-vascular endothelial growth factor (anti-VEGF) agents, and attempt to provide treatment guidance. Areas covered: An Embase search was conducted using the terms 'anti-VEGF', 'pegaptanib', 'ranibizumab', 'bevacizumab', 'aflibercept'...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1404987

    authors: Edington M,Connolly J,Chong NV

    更新日期:2017-12-01 00:00:00

  • Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review.

    abstract:INTRODUCTION:Pediatric critical illness and associated alterations in organ function can change drug pharmacokinetics (PK). Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for severe cardiac and/or respiratory failure, causes additional PK alterations that affect drug disposition. AREAS COVERED:The p...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2016.1201066

    authors: Himebauch AS,Kilbaugh TJ,Zuppa AF

    更新日期:2016-10-01 00:00:00

  • Biomarkers of immunosuppressant organ toxicity after transplantation: status, concepts and misconceptions.

    abstract:INTRODUCTION:A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but sometimes also exhibit limiting side effects. The key to improving long-term outcome following transplantation is the selection o...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.544249

    authors: Christians U,Klawitter J,Klawitter J,Brunner N,Schmitz V

    更新日期:2011-02-01 00:00:00

  • Evaluation of the pharmacokinetics, preclinical and clinical efficacy of pralatrexate for the treatment of T-cell lymphoma.

    abstract:INTRODUCTION:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of T-cell neoplasms. Most patients with PTCL have a poor outcome with conventional therapies and are not cured without stem-cell transplantation. Pralatrexate, a novel antifolate chemotherapeutic agent, was rationally designed to impede folate m...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.595404

    authors: Foss FM

    更新日期:2011-09-01 00:00:00

  • Deferasirox: pharmacokinetics and clinical experience.

    abstract:INTRODUCTION:Iron overload is an inevitable consequence of transfusion therapy for a variety of underlying anemias. Iron overload, without effective chelation, will lead to significant morbidity and mortality. Deferasirox (Exjade®) is an oral tridentate iron chelator used for reducing iron overload. AREAS COVERED:In a...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2012.640674

    authors: Galanello R,Campus S,Origa R

    更新日期:2012-01-01 00:00:00

  • Pharmacokinetic properties and drug interactions of apigenin, a natural flavone.

    abstract:INTRODUCTION:Apigenin, a natural flavone, is widely distributed in plants such as celery, parsley and chamomile. It is present principally as glycosylated in nature. Higher intake of apigenin could reduce the risk of chronic diseases. It has gained particular interest in recent years as a beneficial, health-promoting a...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1251903

    authors: Tang D,Chen K,Huang L,Li J

    更新日期:2017-03-01 00:00:00

  • Therapeutic use of the phosphate binder lanthanum carbonate.

    abstract::Hyperphosphatemia is recognized as a principal mineral disorder in chronic kidney disease (CKD) that leads to the development of secondary hyperparathyroidism. Recent data indicate that hyperphosphatemia is associated with accelerated cardiac calcification and increased mortality in patients with CKD. Control of serum...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425250802614886

    authors: Barton Pai A,Conner TA,McQuade CR

    更新日期:2009-01-01 00:00:00

  • In vitro cell culture models for the assessment of pulmonary drug disposition.

    abstract:BACKGROUND:Aerosol administration of therapeutics to the respiratory system represents a significant opportunity for many classes of drugs, both small molecules and macromolecules, including recently engineered peptide and protein therapeutics. However, minimally invasive assessment of drug absorption mechanisms in viv...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.4.4.333

    authors: Sporty JL,Horálková L,Ehrhardt C

    更新日期:2008-04-01 00:00:00

  • The regulation of human hepatic drug transporter expression by activation of xenobiotic-sensing nuclear receptors.

    abstract:INTRODUCTION:If a drug is found to be an inducer of hepatic drug metabolizing enzymes via activation of nuclear receptors such as pregnane X receptor (PXR) or constitutive androstane receptor (CAR), it is likely that drug transporters regulated through these same receptors will be induced as well. This review highlight...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2016.1223626

    authors: Amacher DE

    更新日期:2016-12-01 00:00:00

  • The impact of advancing age on P-glycoprotein expression and activity: current knowledge and future directions.

    abstract::With the progressive ageing of the population, an increasing number of elderly patients are being exposed to multiple drugs because of co-existing morbidity states requiring pharmacological management. However, the knowledge of the effects of ageing on the pharmacokinetics and pharmacodynamics of individual drugs is f...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 社论,评审

    doi:10.1517/17425255.3.3.315

    authors: Mangoni AA

    更新日期:2007-06-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of insulin glargine 300 U/mL in the treatment of diabetes and their clinical relevance.

    abstract:INTRODUCTION:A more concentrated insulin glargine formulation, containing 300 U/mL (Gla-300) was approved in 2015 in the US and Europe for the treatment of diabetes mellitus in adults. AREAS COVERED:This drug evaluation focuses on the pharmacokinetics (PK) and pharmacodynamics (PD) of Gla-300 from studies published up...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2016.1202916

    authors: Owens DR

    更新日期:2016-08-01 00:00:00

  • Updated pharmacokinetic considerations for the use of antimalarial drugs in pregnant women.

    abstract:INTRODUCTION:The association between pregnancy and altered drug pharmacokinetic (PK) properties is acknowledged, as is its impact on drug plasma concentrations and thus therapeutic efficacy. However, there have been few robust PK studies of antimalarial use in pregnancy. Given that inadequate dosing for prevention or t...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1080/17425255.2020.1802425

    authors: Moore BR,Davis TM

    更新日期:2020-09-01 00:00:00

  • Sertindole: pharmacological and clinical profile and role in the treatment of schizophrenia.

    abstract:BACKGROUND:Sertindole is a second-generation antipsychotic recently reintroduced in the market for the treatment of schizophrenia after a reevaluation of its risks and benefits. OBJECTIVE:This article provides an overview of the pharmacological properties of sertindole as well as of its efficacy, tolerability and safe...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.4.5.629

    authors: Spina E,Zoccali R

    更新日期:2008-05-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of oral anticoagulants used in atrial fibrillation.

    abstract:INTRODUCTION:The availability of non-vitamin K antagonist oral anti-coagulants alongside vitamin K antagonists has offered a variety of options for anti-coagulation, but has also necessitated a good understanding of the pharmacological properties of each of these drugs prior to their use, to maximise the therapeutic be...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2019.1604686

    authors: Fawzy AM,Lip GYH

    更新日期:2019-05-01 00:00:00

  • The pharmacokinetic evaluation of boceprevir for treatment of hepatitis C virus.

    abstract:INTRODUCTION:Boceprevir is an NS3/NS4A serine protease inhibitor that was approved for use in Hepatitis C virus (HCV) genotype 1 patients by the US Food and Drug Administration (FDA) in May 2011. The approval of this protease inhibitor marked a major paradigm shift in the treatment of HCV, as it was one of the first of...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.840290

    authors: Shankar H,Bichoupan K,Dieterich DT

    更新日期:2013-12-01 00:00:00

  • Ethnic differences in drug metabolism and toxicity from chemotherapy.

    abstract::There is wide inter-individual variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs. Recent evidence suggests that there is even greater variability between individuals of different ethnicity. Allelic variants of genes encoding drug metabolising enzymes are expressed with different i...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425250902800153

    authors: Phan VH,Moore MM,McLachlan AJ,Piquette-Miller M,Xu H,Clarke SJ

    更新日期:2009-03-01 00:00:00

  • CYP3A activity: towards dose adaptation to the individual.

    abstract:INTRODUCTION:Co-medication, gene polymorphisms and co-morbidity are main causes for high variability in expression and function of the CYP3A isoenzymes. Pharmacokinetic variability is a major source of interindividual variability of drug effect and response of CYP3A substrates. While CYP3A genotyping is of limited use,...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2016.1163337

    authors: Hohmann N,Haefeli WE,Mikus G

    更新日期:2016-05-01 00:00:00

  • Assays and applications in warfarin metabolism: what we know, how we know it and what we need to know.

    abstract:INTRODUCTION:Coumadin (R/S-warfarin) is the most widely prescribed oral anticoagulant in the world; nevertheless, its clinical use is complicated by unpredictability in dose requirements to achieve and maintain optimal anticoagulation. Variations in warfarin metabolism among patients contribute to unpredictability in t...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.576247

    authors: Jones DR,Miller GP

    更新日期:2011-07-01 00:00:00

  • Impact of disease, drug and patient adherence on the effectiveness of antiviral therapy in pediatric HIV.

    abstract:INTRODUCTION:Maintaining effective antiretroviral treatment for life is a major problem in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1277203

    authors: Piana C,Danhof M,Della Pasqua O

    更新日期:2017-05-01 00:00:00