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 be altered. Decreased albumin and alpha(1)-acid glycoprotein concentrations during pregnancy will result in decreased protein binding for highly bound drugs. For drugs metabolised by the liver, this can result in misinterpretation of total plasma concentrations of low extraction ratio drugs and overdosing of high extraction ratio drugs administered by non-oral routes. Renal clearance and the activity of the CYP isozymes, CYP3A4, 2D6 and 2C9, and uridine 5'-diphosphate glucuronosyltransferase are increased during pregnancy. In contrast, CYP1A2 and 2C19 activity is decreased. The dose of a drug an infant receives during breastfeeding is dependent on the amount excreted into the breast milk, the daily volume of milk ingested and the average plasma concentration of the mother. The lipophilicity, protein binding and ionisation properties of a drug will determine how much is excreted into the breast milk. The milk to plasma concentration ratio has large inter- and intrasubject variability and is often not known. In contrast, protein binding is usually known. An extensive literature review was done to identify case reports including infant concentrations from breast-fed infants exposed to maternal drugs. For drugs that were at least 85% protein bound, measurable concentrations of drug in the infant did not occur if there was no placental exposure immediately prior to or during delivery. Knowledge of the protein binding properties of a drug can provide a quick and easy tool to estimate exposure of an infant to medication from breastfeeding.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Anderson GDdoi
10.1517/17425255.2.6.947subject
Has Abstractpub_date
2006-12-01 00:00:00pages
947-60issue
6eissn
1742-5255issn
1744-7607journal_volume
2pub_type
杂志文章,评审abstract:INTRODUCTION:The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicte...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1037278
更新日期:2015-01-01 00:00:00
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
更新日期:2020-08-01 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: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::Introduction: Chemokine receptors are important therapeutic targets for the treatment of many human diseases. This study will provide an overview of approved chemokine receptor antagonists and promising candidates in advanced clinical trials.Areas covered: We will describe clinical aspects of chemokine receptor antago...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1711884
更新日期:2020-01-01 00:00:00
abstract:INTRODUCTION:The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2020.1789591
更新日期:2020-09-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:genetic and pharmacologically-driven variations in common mechanisms involved in the disposition of antidepressant medications may contribute to variable interpatient response. This review describes the pharmacological properties underlying the safety and efficacy of desvenlafaxine, a second-gen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2010.535810
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:First- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, icotinib, and afatinib are the standard-of-care for first-line therapy of non-small-cell lung cancer (NSCLC) harboring activating EGFR mutations. Unfortunately, after initial ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1401064
更新日期:2017-12-01 00:00:00
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
更新日期:2018-01-01 00:00:00
abstract:INTRODUCTION:Drug ototoxicity represents one of the main preventable causes of deafness. Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, antimalarial medications, loop diuretics, platinum-based chemotherapeutic agents, some NSAIDs and most recently described, acetaminophen when abused with na...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.614231
更新日期:2011-12-01 00:00:00
abstract::Introduction: The inclusion of pharmacogenetics alongside clinical information in anticoagulant therapy offers the opportunity for a tailored approach to treatment according to individual patient characteristics. Areas covered: Literature was searched using PubMed database, focusing on pharmacogenetics of oral anticoa...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1623878
更新日期:2019-06-01 00:00:00
abstract:INTRODUCTION:Various trials have attempted to develop gene expression profiles (GEPs) that may provide a better predictor of clinical outcome over traditional clinicopathological criteria. AREAS COVERED:The review focuses on two main areas: trials examining chemotherapy-induced GEP changes pre- and post-treatment, and...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.694867
更新日期:2012-09-01 00:00:00
abstract:INTRODUCTION:Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. AREAS COVERED:The purpose of this work is to critically review original data as well as previous reviews an...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章
doi:10.1080/17425255.2021.1836157
更新日期:2021-01-01 00:00:00
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
更新日期:2011-07-01 00:00:00
abstract::It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiolo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425250903176421
更新日期:2009-11-01 00:00:00
abstract:INTRODUCTION:The fixed-dose combination therapy of sofosbuvir (SOF) plus velpatasvir (VEL) is the first pangenotypic, direct-acting antiviral (DAA), single-treatment regimen (STR) for the treatment of hepatitis C virus (HCV) infection to be commercialized. It is approved for the treatment of HCV genotypes 1, 2, 3, 4, 5...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2017.1292253
更新日期:2017-04-01 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:INTRODUCTION:Gestational diabetes mellitus (GDM) complicates 10% of all pregnancies and is defined as hyperglycemia first noted during pregnancy. Rates of GDM are rising and untreated GDM results in complications for both mother and fetus. GDM is often managed by diet and exercise but 30-40% of women will require pharm...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2016.1187131
更新日期:2016-06-01 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:INTRODUCTION:Medication of pregnant women is increasingly common in developed countries. Several placental drug transporters have been shown to transfer their substrates from the trophoblast back to the maternal circulation, thus hindering the transplacental passage of xenobiotics and protecting the fetus. However, the...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1005073
更新日期:2015-04-01 00:00:00
abstract:INTRODUCTION:Adverse drug reactions with an immune pathogenesis are a problem in the clinic and an impediment to drug development. T lymphocytes are believed to play a role in the pathogenesis; however, the nature of the drug interaction with immune receptors remains an area of debate. AREAS COVERED:This article revie...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.992780
更新日期:2015-03-01 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:INTRODUCTION:DNA damaging drugs are widely used for the chemotherapeutic treatment of high-grade osteosarcoma (HGOS). In HGOS patients, several germline polymorphisms have been reported to impact on the development of adverse toxic events related to DNA damaging drugs treatment. Some of these polymorphisms, when presen...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2019.1588885
更新日期:2019-04-01 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
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
更新日期:2006-06-01 00:00:00
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
更新日期:2017-03-01 00:00:00
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
更新日期:2008-12-01 00:00:00
abstract::Acetaminophen (APAP) hepatotoxicity is currently the single most important cause of acute liver failure in the US, and is associated with a significant number of deaths. The toxic response to APAP is triggered by a highly reactive metabolite N-acetyl-p-benzoquinone-imine. Following the hepatocellular initiation events...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2.4.493
更新日期:2006-08-01 00:00:00
abstract:INTRODUCTION:Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy accounting for a significant percentage of thyroid cancer-related fatal events. Traditional treatment modalities used in the other types of thyroid carcinomas have been proved largely ineffective in advanced MTC. Better understanding of the m...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.885015
更新日期:2014-03-01 00:00:00
abstract:INTRODUCTION:Cervical cancer is the second-most common malignancy in women worldwide. Cisplatin was introduced as a radiosensitizer in 1999 to improve chances of survival. Tumor cell hypoxia, however, remains a major limiting factor in the treatment of solid tumors with chemotherapy and radiation. There has since been ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.730518
更新日期:2012-12-01 00:00:00