Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions.

Abstract:

INTRODUCTION:Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic factors include single nucleotide polymorphisms (SNPs) that change OATP activity and epigenetic regulation that modify OATP expression levels. SNPs in OATPs contribute to ADRs. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver diseases such as non-alcoholic fatty liver disease, cholestasis and hepatocellular carcinoma change the expression of multiple OATP isoforms. The role of liver diseases in the occurrence of ADRs is unknown. AREAS COVERED:This article covers the roles OATPs play in ADRs when considered in the context of genetic or environmental factors. The reader will gain a greater appreciation for the current evidence regarding the salience and importance of each factor in OATP-mediated ADRs. EXPERT OPINION:A SNP in a single OATP transporter can cause changes in drug pharmacokinetics and contribute to ADRs but, because of overlap in substrate specificities, there is potential for compensatory transport by other OATP isoforms. By contrast, the expression of multiple OATP isoforms is decreased in liver diseases, reducing compensatory transport and thereby increasing the probability of ADRs. To date, most research has focused on the genetic factors in OATP-mediated ADRs while the impact of environmental factors has largely been ignored.

authors

Clarke JD,Cherrington NJ

doi

10.1517/17425255.2012.656087

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

349-60

issue

3

eissn

1742-5255

issn

1744-7607

journal_volume

8

pub_type

杂志文章,评审
  • The role of pathology in the identification of drug-induced hepatic toxicity.

    abstract::Pathologists play a central role in the recognition and prevention of drug-induced toxicity. Pathologists engaged in clinical practice must identify a pattern of histological lesions that are interpreted in concert with a variety of clinical data to determine the probability of drug-induced toxicity versus background ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2.2.241

    authors: Cullen JM,Miller RT

    更新日期:2006-04-01 00:00:00

  • Direct thrombin inhibition with bivalirudin as an antithrombotic strategy in general and interventional cardiology.

    abstract::Antithrombotic therapy is a crucial component of interventional cardiology and currently involves the administration of both anticoagulant and antiplatelet agents. The implementation of standard dual or triple antiplatelet therapies has allowed percutaneous coronary intervention (PCI) with stent implantation to become...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425225.3.4.609

    authors: Ahrens I,Smith BK,Bode C,Peter K

    更新日期:2007-08-01 00:00:00

  • Improvements in the reliability of in vitro genotoxicity testing.

    abstract:INTRODUCTION:In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53-competent human cel...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.627855

    authors: Kirkland D

    更新日期:2011-12-01 00:00:00

  • Sumatriptan: a review of its pharmacokinetics, pharmacodynamics and efficacy in the acute treatment of migraine.

    abstract:INTRODUCTION:Sumatriptan was developed more than 20 years ago as a 5-HT1B/1D receptor agonist, the first drug in a new class of specific anti-migraine drugs, the triptans. A large amount of information and experience has been gained from the clinical trials undertaken as well the various formulations of sumatriptan use...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.744394

    authors: Tfelt-Hansen P,Hougaard A

    更新日期:2013-01-01 00:00:00

  • Pharmacokinetics, pharmacodynamics and clinical efficacy of omalizumab for the treatment of asthma.

    abstract:INTRODUCTION:Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen. Area covered...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2016.1248403

    authors: Luu M,Bardou M,Bonniaud P,Goirand F

    更新日期:2016-12-01 00:00:00

  • Microdialysis for assessing intratumoral drug disposition in brain cancers: a tool for rational drug development.

    abstract:IMPORTANCE OF THE FIELD:many promising targeted agents and combination therapies are being investigated for brain cancer. However, the results from recent clinical trials have been disappointing. A better understanding of the disposition of drug in the brain early in drug development would facilitate appropriate channe...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2010.523420

    authors: Blakeley J,Portnow J

    更新日期:2010-12-01 00:00:00

  • The use of accelerator mass spectrometry to obtain early human ADME/PK data.

    abstract::There is an increasing recognition within the pharmaceutical industry of the importance of the ADME studies in drug registration. Consequently, there has been a drive in recent times to conduct the ADME studies as early as possible in the development programme. There are, however, regulatory barriers, particularly in ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.1.1.23

    authors: Lappin G,Garner RC

    更新日期:2005-06-01 00:00:00

  • The use of pharmacokinetics in dose individualization of factor VIII in the treatment of hemophilia A.

    abstract:INTRODUCTION:Hemophilia A is a bleeding disorder resulting from a lack of clotting factor VIII (FVIII), and treatment typically consists of prophylactic replacement of the deficient factor. However, high between subject variability precludes the development of a 'one size fits all' dosing strategy and necessitates an i...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1080/17425255.2016.1214711

    authors: McEneny-King A,Iorio A,Foster G,Edginton AN

    更新日期:2016-11-01 00:00:00

  • Telmisartan in the treatment of hypertension.

    abstract:BACKGROUND:Telmisartan is an orally active angiotensin II receptor antagonist prescribed once daily. OBJECTIVE:To evaluate the efficacy of telmisartan on blood pressure control, and on other end points, when given as monotherapy or in combination. METHODS:Review of published literature. RESULTS:Telmisartan produces ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.4.4.485

    authors: Rosario BH,Hendra TJ

    更新日期:2008-04-01 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

  • Pharmacokinetic drug evaluation of ixazomib citrate for the treatment of multiple myeloma.

    abstract:INTRODUCTION:multiple myeloma (MM) is a plasma cell disorder that represents the second most frequent hematologic cancer. Although MM is still an incurable disease, prognosis has improved in the last decades thanks to the introduction of novel agents such as proteasome inhibitors (PIs), immunomodulatory drugs, monoclon...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2018.1417388

    authors: Salvini M,Troia R,Giudice D,Pautasso C,Boccadoro M,Larocca A

    更新日期:2018-01-01 00:00:00

  • Metabolomic strategies to identify tissue-specific effects of cardiovascular drugs.

    abstract:BACKGROUND:The number of patients eligible for cardiovascular therapies in general is forecast to increase substantially in the coming decades. However, the current list of potential future cardiovascular blockbuster drugs is alarmingly short. There is thus a clear need for innovative strategies to increase the efficie...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.4.6.665

    authors: Jänis MT,Laaksonen R,Oresic M

    更新日期:2008-06-01 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

  • Fondaparinux in acute coronary syndromes.

    abstract::Antithrombotic therapies form the cornerstone of management of acute coronary syndromes (ACS). An ideal antithrombotic agent should reduce ischemic complications while keeping bleeding events to a minimum. Heparins, both unfractionated and low molecular weight, reduce ischemic outcomes but also significantly increase ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425250903456039

    authors: Chaturvedi V,Karthikeyan G

    更新日期:2009-12-01 00:00:00

  • How is sesamin metabolised in the human liver to show its biological effects?

    abstract:INTRODUCTION:Sesamin is a major lignan found in sesame and is known to have various biological effects. Some of these biological effects occur following its metabolic conversion to corresponding catechols and, therefore, the study of sesamin metabolism is quite important. There is currently a need to identify the enzym...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2012.637917

    authors: Yasuda K,Sakaki T

    更新日期:2012-01-01 00:00:00

  • The influence of pharmacogenetics and cofactors on clinical outcomes in kidney transplantation.

    abstract:INTRODUCTION:Immunosuppressive drugs have a narrow therapeutic range and large inter-individual response variability. This has prompted pharmacogenetic studies, mostly with regard to their dose-concentration relationships, but also about proteins involved in their pharmacodynamics. Some polymorphisms of genes involved ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.570260

    authors: Picard N,Marquet P

    更新日期:2011-06-01 00:00:00

  • Safety considerations for patients with epilepsy taking antiepileptic drugs alongside caffeine or other methylxanthine derivatives.

    abstract:INTRODUCTION:Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy. However, ∼ 30% of patients do not remain seizure free. It is possible that methylxanthine derivatives (e.g., caffeine and theophylline) may partially account for this outcome. AREAS COVERED:Data on the convulsive activity of methylx...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2014.920822

    authors: Chrościńska-Krawczyk M,Radzik I,Miziak B,Czuczwar SJ

    更新日期:2014-07-01 00:00:00

  • The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients.

    abstract:INTRODUCTION:Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual resp...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1080/17425255.2016.1209482

    authors: Tverdohleb T,Dinc B,Knezevic I,Candido KD,Knezevic NN

    更新日期:2016-11-01 00:00:00

  • Therapeutic drug monitoring of antiepileptic drugs: current status and future prospects.

    abstract::Introduction: Antiepileptic drugs (AEDs) are the cornerstone of treatment of patients with epilepsy, and there are presently 27 licensed AEDs making AEDs among the most common medications for which therapeutic drug monitoring (TDM) is performed. The aim of this review is to provide an overview of the current evidence ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2020.1724956

    authors: Johannessen Landmark C,Johannessen SI,Patsalos PN

    更新日期:2020-03-01 00:00:00

  • The role of oseltamivir in the treatment and prevention of influenza in children.

    abstract::The burden of seasonal influenza in children is poorly recognized, in spite of the potential for severe and even life-threatening illness and common secondary complications. Children are a primary reservoir for the spread of influenza to both family members and the community, which imposes a sizeable social and econom...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.3.5.755

    authors: Whitley RJ

    更新日期:2007-10-01 00:00:00

  • Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies.

    abstract:INTRODUCTION:Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs that inhibit the pro-inflammatory effects of lipopolysaccharide (LPS) and improve outcome when added to conventional sepsis treatments are lacking. Eritoran tetrasodium (E5564) is a promising candidate t...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.558190

    authors: Barochia A,Solomon S,Cui X,Natanson C,Eichacker PQ

    更新日期:2011-04-01 00:00:00

  • Pharmacokinetic and pharmacodynamic evaluation of panitumumab in the treatment of colorectal cancer.

    abstract:INTRODUCTION:Integration of targeted therapy and additional chemotherapy options has improved median overall survival (OS) in patients with unresectable metastatic colorectal cancer (mCRC). Cetuximab and panitumumab are examples of targeted therapies, specifically against the epidermal growth factor receptor (EGFR). Th...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2015.1112787

    authors: Lo L,Patel D,Townsend AR,Price TJ

    更新日期:2015-01-01 00:00:00

  • Using pharmacokinetics to predict the effects of pregnancy and maternal-infant transfer of drugs during lactation.

    abstract::Knowledge of pharmacokinetics and the use of a mechanistic-based approach can improve our ability to predict the effects of pregnancy for medications when data are limited. Despite the many physiological changes that occur during pregnancy that could theoretically affect absorption, bioavailability does not appear to ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2.6.947

    authors: Anderson GD

    更新日期:2006-12-01 00:00:00

  • Piperine-mediated drug interactions and formulation strategy for piperine: recent advances and future perspectives.

    abstract:INTRODUCTION:Piperine has various pharmacological effects and can modulate the functional activity of metabolic enzymes and drug transporters. Consequently, there is a great interest in the application of piperine as an alternative medicine or bioavailability enhancer. Areas covered: This review deals with the effects ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2018.1418854

    authors: Lee SH,Kim HY,Back SY,Han HK

    更新日期:2018-01-01 00:00:00

  • The potential protein-mediated hepatic uptake: discussion on the molecular interactions between albumin and the hepatocyte cell surface and their implications for the in vitro-to-in vivo extrapolations of hepatic clearance of drugs.

    abstract::Introduction: In quantitative modeling, the resolving of underpredictions and overpredictions of hepatic clearance (CLh) makes a top priority for pharmacokinetic modelers. Clearly, the 'protein-mediated hepatic uptake' is a violation of 'the free drug hypothesis', but the lack of its consideration in CLh-predictive ap...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2019.1640679

    authors: Bteich M,Poulin P,Haddad S

    更新日期:2019-08-01 00:00:00

  • Picoplatin pharmacokinetics and chemotherapy of non-small cell lung cancer.

    abstract:INTRODUCTION:Picoplatin was developed as platinum coordination complex to overcome development of resistance, through conjugation to thioles, by the introduction of a methyl-pyridine moiety into the cisplatin parent structure. Pharmacokinetic parameters of the drug, after intravenous and oral application, were studied ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.815724

    authors: Hamilton G

    更新日期:2013-10-01 00:00:00

  • Prediction of cis-regulatory elements for drug-activated transcription factors in the regulation of drug-metabolising enzymes and drug transporters.

    abstract::The expression of drug-metabolising enzymes is affected by many endogenous and exogenous factors, including sex, age, diet and exposure to xenobiotics and drugs. To understand fully how the organism metabolises a drug, these alterations in gene expression must be taken into account. The central process, the definition...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2.3.367

    authors: Podvinec M,Meyer UA

    更新日期:2006-06-01 00:00:00

  • GLP-1 agonists for type 2 diabetes: pharmacokinetic and toxicological considerations.

    abstract:INTRODUCTION:Within recent years, glucagon-like peptide 1 receptor agonists (GLP-1-RA) have emerged as a new treatment option for type 2 diabetes. The GLP-1-RA are administered subcutaneously and differ substantially in pharmacokinetic profiles. AREAS COVERED:This review describes the pharmacokinetics and safety aspec...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.731394

    authors: Jespersen MJ,Knop FK,Christensen M

    更新日期:2013-01-01 00:00:00

  • Soft gel capsules improve melatonin's bioavailability in humans.

    abstract:OBJECTIVE:Oral bioavailability is one of the most important properties in drug design and development. A poor oral bioavailability can result in low efficacy and unpredictable response to a drug. Several dosages of melatonin have been used for various investigations to clarify its bioavailability in humans. Aiming to s...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章

    doi:10.1517/17425255.2014.943183

    authors: Proietti S,Carlomagno G,Dinicola S,Bizzarri M

    更新日期:2014-09-01 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