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 in their disposition pathways were shown to affect their dose-concentration relationships. The impact of pharmacogenetics on tissue distribution and the resulting clinical effects have less often been studied. More importantly, a few single nucleotide polymorphisms seem to have a significant impact on the incidence of acute rejection or the adverse effects of immunosuppressants. Environmental factors often interact with such genotype-phenotype relationships. AREAS COVERED:This article reviews the impact of genetic polymorphisms of the metabolic enzymes, membrane transporters and target proteins of mycophenolic acid, calcineurin inhibitors and mammalian target of rapamycin inhibitors on clinical outcomes in kidney transplantation. EXPERT OPINION:The current level of evidence is not yet high enough to recommend pharmacogenetic personalization of immunosuppressive regimens in transplant recipients. The prevention of cellular toxicity associated with local metabolism or transport, which cannot be addressed by routine monitoring, is worth investigating further.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Picard N,Marquet Pdoi
10.1517/17425255.2011.570260subject
Has Abstractpub_date
2011-06-01 00:00:00pages
731-43issue
6eissn
1742-5255issn
1744-7607journal_volume
7pub_type
杂志文章,评审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
更新日期:2016-08-01 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: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:Telaprevir is one of the first direct-acting antiviral drugs approved for the treatment of the hepatitis C virus (HCV) genotype 1. Following its approval in 2011, new data regarding the pharmacokinetics and pharmacodynamics were reported, leading to important clinical applications. AREAS COVERED:This arti...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1049532
更新日期:2015-07-01 00:00:00
abstract:INTRODUCTION:Therapeutic hypothermia is being employed clinically due to its neuro-protective benefits. Both critical illness and therapeutic hypothermia significantly affect drug disposition, potentially contributing to drug-therapy and drug-disease interactions. Currently, there is limited information on the known al...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.574127
更新日期:2011-07-01 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:BACKGROUND:A growing body of evidence suggests that everolimus might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the post-transplant patient. OBJECTIVE:To summarize the emerging evidence for emplo...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.4.6.807
更新日期:2008-06-01 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: The target concentration strategy uses PKPD information for dose determination. Models have also quantified exposure-response relationships, improved understanding of developmental pharmacokinetics, rationalized dose prescription, provided insight into the importance of covariate information, explained d...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2020.1739648
更新日期:2020-04-01 00:00:00
abstract::Toxicogenomics is the application of gene expression profiling technology to toxicology. This results in the generation of very large and complex gene expression data sets associated with the development of toxicities. It is widely assumed that this data can be deconvoluted to reveal novel insights into toxicological ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.1.2.247
更新日期:2005-08-01 00:00:00
abstract:INTRODUCTION:Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despi...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1080/17425255.2018.1441285
更新日期:2018-03-01 00:00:00
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::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: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
更新日期:2010-12-01 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
abstract:INTRODUCTION:Epilepsy is a chronic neurological disease manifesting as recurrent seizures. Despite the availability of numerous antiepileptic drugs (AEDs), one-third of the patients are not responsive to treatment. Such inter-individual variability in the response to AEDs may be partly explained by genetic differences....
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2014.872630
更新日期:2014-03-01 00:00:00
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
更新日期:2006-12-01 00:00:00
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
更新日期:2010-01-01 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: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:The key feature of the newborn is its fast age-dependent maturation, resulting in extensive variability in pharmacokinetics and -dynamics, further aggravated by newly emerging covariates like treatment modalities, environmental issues or pharmacogenetics. This makes clinical research in neonates relevant a...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2015.1046433
更新日期:2015-07-01 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:INTRODUCTION:Recent advances in molecular biology have enabled personalized cancer therapies with molecularly targeted agents (MTAs), which offer a promising future for cancer therapy. Dynamic modeling and simulation (M&S) is a powerful mathematical approach linking drug exposures to pharmacological responses, providin...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2016.1141895
更新日期:2016-01-01 00:00:00
abstract:INTRODUCTION:Emtricitabine/tenofovir disoproxil fumarate fixed-dose combination (FTC/TDF FDC) is the co-formulation of a nucleoside and a nucleotide, respectively. After oral administration, both drugs exhibit plasma and intracellular half-lives suitable for once-daily dosing. Within the host cells, active metabolites ...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.714367
更新日期:2012-10-01 00:00:00
abstract:INTRODUCTION:Pharmacokinetic and pharmacodynamic drug interactions (DIs) can occur between antiepileptics (AEDs) and second-generation antipsychotics (SGAPs). Some AED and SGAP pharmacodynamic mechanisms are poorly understood. AED-SGAP combinations are used for treating comorbid illnesses or increasing efficacy, partic...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2012.660918
更新日期:2012-03-01 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: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
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Despite increasing early detection and treatment of prostate cancer, a subset of patients presents with or develops metastatic disease. Androgen deprivation therapy is effective but resistance eventually develops, resulting in a lethal phenotype known as castration-resistant prostate cancer (CRPC). Recentl...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2013.789019
更新日期:2013-07-01 00:00:00
abstract:INTRODUCTION:Pemphigus is an autoimmune blistering disease of the skin and mucous membranes characterized by the development of autoantibodies against the desmosomal proteins, desmoglein-1 and -3. Before the advent of corticosteroids, therapy was almost fatal. The introduction of high-dose corticosteroid therapy has re...
journal_title:Expert opinion on drug metabolism & toxicology
pub_type: 杂志文章,评审
doi:10.1517/17425255.2011.542149
更新日期:2011-02-01 00:00:00
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
更新日期:2011-02-01 00:00:00