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, direct testing of enzyme function ('phenotyping') may be more promising to achieve individualized dosing of CYP3A substrates. AREAS COVERED:We will discuss available phenotyping strategies for CYP3A isoenzymes and causes of intra- and interindividual variability of CYP3A. The impact of phenotyping on the dose selection and pharmacokinetics of CYP3A substrates (docetaxel, irinotecan, tyrosine kinase inhibitors, ciclosporin, tacrolimus) are reviewed. Pubmed searches were conducted during March-November 2015 to retrieve articles related to CYP3A enzyme, phenotyping, drug interactions with CYP3A probe substrates, and phenotyping-guided dosing algorithms. EXPERT OPINION:While ample data is available on the choice appropriate phenotyping drugs (midazolam, alfentanil, aplrazolam, buspirone, triazolam), less clinical trial data is available concerning strategies to usefully guide dosing in the clinical practice. Implementation into the clinical routine necessitates further research to identify (1) an easy-to-use and cheap test for CYP3A activity that (2) adequately predicts drug exposure to (3) allow a sound decision on dose adaptation and hence (4) improve clinical outcome and/or reduce the intensity or frequency of adverse drug effects.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Hohmann N,Haefeli WE,Mikus Gdoi
10.1517/17425255.2016.1163337subject
Has Abstractpub_date
2016-05-01 00:00:00pages
479-97issue
5eissn
1742-5255issn
1744-7607journal_volume
12pub_type
杂志文章,评审abstract::Luminogenic cytochrome P450 (CYP) assays couple CYP enzyme activity to firefly luciferase luminescence in a technology called P450-Glo(TM) (Promega). Luminogenic substrates are used in assays of human CYP1A1, -1A2, -1B1, -2C8, -2C9, -2C19, -2D6, -2J2, -3A4, -3A7, -4A11, -4F3B, -4F12 and -19. The assays detect dose-dep...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.629
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVES:A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar). RESEARCH DESIGN AND METHODS:In this controlled, single-center study, 66 type ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,随机对照试验
doi:10.1517/17425255.2015.1058779
更新日期:2015-01-01 00:00:00
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
更新日期:2007-06-01 00:00:00
abstract::The pharmaceutical relevance of proton-coupled peptide transporters is currently under intense investigation in many laboratories. Studies have shown that these membrane proteins, expressed in intestine, kidney, choroid plexus and other tissues, accept many peptidomimetic drugs and prodrugs as substrates. The focus of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903042292
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:Carboxylesterases (CEs) are ubiquitous enzymes responsible for the hydrolysis of numerous clinically useful drugs. As ester moieties are frequently included in molecules to improve their water solubility and bioavailability, de facto they become substrates for CEs. OBJECTIVE:In this review, we describe the ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.9.1153
更新日期:2008-09-01 00:00:00
abstract::Valproate (2-propylpentanoate) is available as valproic acid, sodium valproate and semisodium valproate. It has actions on dopamine, GABA and glutamate neurotransmission and intracellular signaling. Its main psychiatric use is to treat bipolar disorder. It has been used in other psychiatric disorders, including schizo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902911455
更新日期:2009-05-01 00:00:00
abstract:INTRODUCTION:Short- and long-acting β agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degr...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.939956
更新日期:2014-09-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:There has been much interest in generating gene signatures to predict treatment response in breast cancer. AREAS COVERED IN THIS REVIEW:There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline stu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903510611
更新日期:2010-03-01 00:00:00
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
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:Chronic low back pain (CLBP) is a common and difficult illness to manage. Some individuals with CLBP have pain processing disorders and are also at risk for opioid abuse, misuse; addiction and diversion. Guidelines have been published to guide management; neuromodulation, exercise, mindfulness-based stress...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1191469
更新日期:2016-07-01 00:00:00
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
更新日期:2011-04-01 00:00:00
abstract:BACKGROUND:Testosterone replacement therapy in hypogonadal men has been used for > 60 years. The use of testosterone substitution is continuously growing and is given to aging men to improve the quality of life. Because testosterone use is associated with muscle strength enhancing effects, it has become a popular drug ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902976862
更新日期:2009-07-01 00:00:00
abstract:INTRODUCTION:The N-acetylation polymorphism has been the subject of comprehensive reviews describing the role of arylamine N-acetyltransferase 2 (NAT2) in the metabolism of numerous aromatic amine and hydrazine drugs. AREAS COVERED:We describe and review data that more clearly defines the effects of NAT2 haplotypes an...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1840551
更新日期:2021-01-01 00:00:00
abstract:INTRODUCTION:Raltegravir was the first available integrase inhibitor for treating HIV-positive patients. This review aims to provide an overview of its role in the management of HIV-1 infection, highlighting its key pharmacokinetic and pharmacodynamic properties. AREAS COVERED:This review covers material searched and ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1056732
更新日期:2015-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Iloperidone is a newly commercialized second-generation (atypical) antipsychotic approved for the acute treatment of schizophrenia in adults. AREAS COVERED IN THIS REVIEW:the purpose of this review is to describe the pharmacokinetic profile of iloperidone and its clinical implications in the tr...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.531259
更新日期:2010-12-01 00:00:00
abstract:OBJECTIVE:To investigate the metabolic routes and metabolites of myricitrin, an important active ingredient of traditional herbal medicine, yielded by the isolated human intestinal bacteria, which have not been reported previously. METHODS:Fresh human fecal samples were collected from a healthy female volunteer and ab...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1517/17425255.2014.918954
更新日期:2014-07-01 00:00:00
abstract::Introduction: Overactive bladder (OAB) has a heterogeneous presentation that varies between individuals and by gender. Treatment with antimuscarinic medications is standard first line pharmacotherapy for most patients with OAB. However, gender specific differences in the pharmacokinetics and pharmacodynamics of antimu...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1714591
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC. OBJECTIVE:To summarize current data on balsalazide and to discuss its impact on management of UC. METHODS:A systematic review o...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903206996
更新日期:2009-10-01 00:00:00
abstract::Three first-line antituberculosis drugs, isoniazid, rifampicin and pyrazinamide, may induce liver injury, especially isoniazid. This antituberculosis drug-induced liver injury ranges from a mild to severe form, and the associated mortality cases are not rare. The major drug-metabolizing enzyme of isoniazid is N-acetyl...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.3.1.1
更新日期:2007-02-01 00:00:00
abstract:INTRODUCTION:The absorption, distribution, metabolism, excretion and toxicity (ADME-tox) processes of drugs are of importance and require preclinical investigation intestine in addition to the liver. Various models have been developed for prediction of ADME-tox in the intestine. In this review, precision-cut intestinal...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1125882
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:There have been increasing concerns regarding adverse reactions and toxicity incidents caused by traditional Chinese medicines (TCMs), among which the nephrotoxicity is particularly worrying. AREAS COVERED:This review summarizes the ingredients with renal toxicity from some TCMs through searching the rele...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1132306
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Topotecan was initially approved for the treatment of recurrent ovarian cancer. In cervical cancer, it has been investigated for its potential as part of systemic therapy for advanced and/or recurrent disease and in combination with cisplatin and radiation as a first-line treatment for advanced disease. As...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.758249
更新日期:2013-02-01 00:00:00
abstract::The in vitro pharmacological profiling of drugs using a large panel of cloned receptors (e.g., G protein-coupled receptors, ligand-gated ion channels, Na(+)-dependent monoamine transporters), an approach that has come to be known as 'receptorome screening', has unveiled novel molecular mechanisms responsible for the a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.3.377
更新日期:2005-10-01 00:00:00
abstract:INTRODUCTION:Multiple myeloma (MM) patients who relapse, or become refractory to currently available novel agents, have limited treatment options with poor outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the immunomodulatory agent pomalidomide have provided new treatment strategies within ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.827169
更新日期:2013-11-01 00:00:00
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
更新日期:2017-12-01 00:00:00
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
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Obesity, hypertension and Type 2 diabetes are major contributing factors to the increase in the number of patients that have chronic kidney disease. The clustering of visceral obesity and cardiovascular risk factors has been designated metabolic syndrome or cardiometabolic syndrome. Cardiometabolic syndrome ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.2.165
更新日期:2008-02-01 00:00:00
abstract:INTRODUCTION:Replacement therapy for FVIII/IX in hemophilia A/B is more than 50 years old following the discovery of cryoprecipitate by Judith Pool in 1964. On-demand therapy and prophylaxis to treat or prevent bleedings is very demanding owing to the short half-life (HL) of factor concentrates (no more than 12-14 h fo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2016.1240168
更新日期:2016-11-01 00:00:00
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
更新日期:2014-12-01 00:00:00
abstract:INTRODUCTION:The prevalence of obesity and associated co-morbid conditions is increasing globally. Physiological changes accompanying obesity are likely to result in altered drug pharmacokinetics; however, there is paucity of information on how to best dose adjust for the obese. AREAS COVERED:This review presents mate...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.570331
更新日期:2011-06-01 00:00:00