Abstract:
BACKGROUND:Anticancer drugs are characterized by a narrow therapeutic window and significant inter-patient variability in therapeutic and toxic effects. Current body surface area (BSA)-based dosing fails to standardize systemic anticancer drug exposure and other alternative dosing strategies also have their limitations. Just as important as the initial dose selection is the subsequent dose revision to ensure the dose is correct. OBJECTIVE:To provide an insight into the different dose individualization and dose adjustment methods, their feasibility and applicability in daily oncology practice and to suggest a practical framework for dose calculation and a basis for future research. METHODS:Review of relevant literature related to dose calculation of anticancer drugs. RESULTS:Strategies using clinical parameters, genotype and phenotype markers, and therapeutic drug monitoring all have potential and each has a role for specific drugs. However, no one method is a practical dose calculation strategy for many or all drugs. CONCLUSION:Given that BSA-dosing leads to significant underdosing it is not reasonable to use this as the sole method of dose calculation. Because of wide disparity in individual patient characteristics and elimination mechanisms, we are unlikely to find the 'Holy Grail' of a single individualized dosing strategy for every patient and anticancer drug in the near future. We propose a pragmatic, although invalidated system for initial dose calculation using dose clusters and structured subsequent dose revision based on treatment-related toxicities and therapeutic drug monitoring. These models need to be tested in clinical trials.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Gao B,Klumpen HJ,Gurney Hdoi
10.1517/17425255.4.10.1307subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1307-19issue
10eissn
1742-5255issn
1744-7607journal_volume
4pub_type
杂志文章,评审abstract:INTRODUCTION:Many different drugs and xenobiotics (chemical compounds foreign to an organism) can injure the bile duct epithelium and cause inflammatory bile duct diseases (cholangiopathies) ranging from transient cholestasis to vanishing bile duct syndrome, sclerosing cholangitis with development of biliary fibrosis a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.674511
更新日期:2012-05-01 00:00:00
abstract::The human ether-a-go-go-related gene (hERG) encodes the pore-forming alpha-subunit of a voltage-gated potassium (K(+)) channel. A variety of unrelated compounds reduce K(+ )current in the heart by blocking the pore or disrupting trafficking of the hERG channel to the membrane surface. This induces a syndrome known as ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.1.81
更新日期:2006-02-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.540238
更新日期:2011-01-01 00:00:00
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
更新日期:2014-07-01 00:00:00
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
更新日期:2007-10-01 00:00:00
abstract:INTRODUCTION:Extensive within-population variability is the essence of neonatal pharmacology. Despite this, infants remain one of the last therapeutic orphans. Together with additional legal initiatives, tailoring of already available tools (modeling, covariates, pharmacovigilance) may significantly improve pharmacothe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.931937
更新日期:2014-08-01 00:00:00
abstract:INTRODUCTION:It is widely accepted that current practice of polypharmacy inevitably increases the incidence of drug-drug interactions (DDIs). Serious DDIs are a major liability for new molecular entities entering the pharmaceutical market. Various strategies are employed to avoid problematic compounds for clinical deve...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1013095
更新日期:2015-04-01 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: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
更新日期:2016-12-01 00:00:00
abstract:INTRODUCTION:Treatments for hepatitis C virus (HCV) infection have advanced rapidly in the last decade. Pegylated interferon alpha 2a (PEG-IFN alpha 2a) alone, in combination with ribavirin and with or without direct acting antivirals (DAAs) is modestly effective in the treatment of chronic HCV infection. Areas covered...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1421173
更新日期:2018-02-01 00:00:00
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
更新日期:2005-06-01 00:00:00
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
更新日期:2011-12-01 00:00:00
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
更新日期:2008-06-01 00:00:00
abstract:INTRODUCTION:The goal of pharmacologic therapy with antiepileptic drugs (AEDs) is to reduce the frequency of seizures and achieve a seizure-free state with minimal side effects. However 30% of patients treated with available AEDs continue to experience uncontrolled seizures. There is still need for new AEDs with enhanc...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1360278
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.557067
更新日期:2011-04-01 00:00:00
abstract:INTRODUCTION:Drug-disease interactions include the impact of a drug and a particular disease condition on each other. However, the current practice in addressing drug-disease interaction is unbalanced and mostly limited to how the drug worsens the disease or health condition. AREAS COVERED:Aspirin and gastric ulcer in...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1201064
更新日期:2016-09-01 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: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:BACKGROUND:The activity of various CYP isoforms is critical for maintaining the clinical effectiveness of many medications. Therefore, determining the sex-dependent activity of clinically relevant CYP families is highly important for optimal therapeutic effectiveness. OBJECTIVE:This review examined the sex-dependent a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.4.413
更新日期:2008-04-01 00:00:00
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
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:Due to their multiple effects, glucocorticoids (GCs) have versatile medical uses. They can regulate many xenobiotic-metabolizing enzymes of the cytochrome P450 (CYP) superfamily, and thus, influence pharmacotherapy. AREAS COVERED:The aim of this paper is to summarize the molecular effects of GCs on CYP as...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.878703
更新日期:2014-03-01 00:00:00
abstract:INTRODUCTION:For orally administered drugs, their intestinal absorption and hepatic metabolism are key players for determining a drug's systemic bioavailability and thus therapeutic effect. Drug absorption and metabolism are both complicated processes, with many physicochemical and physiological factors involved. Under...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.802772
更新日期:2013-10-01 00:00:00
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
更新日期:2017-12-01 00:00:00
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
更新日期:2013-12-01 00:00:00
abstract:INTRODUCTION:Major depressive disorder (MDD), one of the most common disorders in medical practice and one of the leading causes of disability worldwide, is frequently comorbid with anxiety disorders. Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effe...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.904286
更新日期:2014-05-01 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:CYP enzymes from the CYP2C and CYP2J subfamilies metabolize arachidonic acid in a regiospecific and stereoselective manner to eight epoxyeicosatrienoic acids (EETs). Various EETs have been detected in the liver, as well as in many extrahepatic tissues, and have been implicated in numerous physiological funct...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250902932923
更新日期:2009-07-01 00:00:00
abstract::Psychiatric disorders are a leading cause of disability worldwide and despite significant pharmacologic advances, often remain difficult to diagnose correctly and treat fully. Factors which contribute to these difficulties include imprecise understanding of etiology, syndromal nature of many disorders and overlap in d...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 社论
doi:10.1517/17425255.2013.733696
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:The elucidation of the toxicological mechanisms of herbal medicines is becoming more and more important with the increasing application of herbal medicines, for treatment of various diseases and the promotion of health. Furthermore, it is widely recognized that as herbal components undergo bioactivation, t...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.586335
更新日期:2011-08-01 00:00:00
abstract::Severe adverse drug reactions (ADRs) are a major problem in drug development and clinical practice and the most common cause of market withdrawals of drugs. Individualised drug safety aims at the prospective identification of single patients who carry genetic predispositions for the development of serious or fatal ADR...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.3.537
更新日期:2005-10-01 00:00:00