Novel models for assessing blood-brain barrier drug permeation.

Abstract:

INTRODUCTION:The blood-brain barrier (BBB) is a selectively permeable micro-vascular unit which prevents many central nervous system (CNS)-targeted compounds from reaching the brain. A significant problem in CNS drug development is the ability to model BBB permeability in a timely, reproducible and cost-effective manner. Through the years, several models have been used such as artificial membranes, cell culture and animal models. AREAS COVERED:In this focused review, the authors cover novel models which have been developed or are in the process of being developed which can be used in modeling BBB. These models can either be used to determine BBB permeability or whether a compound may be disrupting the BBB. Many of these models lend themselves to high-throughput screening. The main model organisms covered here are the grasshopper (Locusta migratoria), fruit fly (Drosophila melanogaster) and zebrafish (Danio rerio). EXPERT OPINION:Many of the models covered here have only recently been utilized for BBB studies and still needs to be fully studied for its impact on reducing costs during drug development. The strength of these models lay in the fact that a whole organism experiment can be done in high throughput fashion as compared with classical vertebrate models such as micro-dialysis.

authors

Geldenhuys WJ,Allen DD,Bloomquist JR

doi

10.1517/17425255.2012.677433

subject

Has Abstract

pub_date

2012-06-01 00:00:00

pages

647-53

issue

6

eissn

1742-5255

issn

1744-7607

journal_volume

8

pub_type

杂志文章,评审
  • Eicosanoids and renal damage in cardiometabolic syndrome.

    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

    authors: Imig JD

    更新日期:2008-02-01 00:00:00

  • Pharmacokinetic evaluation of vortioxetine for the treatment of major depressive disorder.

    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

    authors: Dubovsky SL

    更新日期:2014-05-01 00:00:00

  • Evaluation of the pharmacokinetics and clinical utility of isavuconazole for treatment of invasive fungal infections.

    abstract:INTRODUCTION:Invasive fungal infections remain a leading cause of infectious morbidity and mortality in immunocompromised patients. There are relatively few effective antifungal agents, and currently available agents all have significant limitations. Isavuconazole is a novel second-generation triazole with broad-spectr...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2012.683859

    authors: Livermore J,Hope W

    更新日期:2012-06-01 00:00:00

  • Role of SLC transporters in toxicity induced by anticancer drugs.

    abstract:INTRODUCTION:. Membrane transporters are integral to the maintenance of cellular integrity of all tissue and cell types. While transporters play an established role in the systemic pharmacokinetics of therapeutic drugs, tissue specific expression of uptake transporters can serve as an initiating mechanism that governs ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2020.1755253

    authors: Huang KM,Uddin ME,DiGiacomo D,Lustberg MB,Hu S,Sparreboom A

    更新日期:2020-06-01 00:00:00

  • Identification of the metabolites of myricitrin produced by human intestinal bacteria in vitro using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

    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

    authors: Du LY,Zhao M,Xu J,Qian DW,Jiang S,Shang EX,Guo JM,Liu P,Su SL,Duan JA,Leng XJ

    更新日期:2014-07-01 00:00:00

  • Experimental models for predicting drug absorption and metabolism.

    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

    authors: Alqahtani S,Mohamed LA,Kaddoumi A

    更新日期:2013-10-01 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

  • Neonatal medicines research: challenges and opportunities.

    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

    authors: Samardzic J,Turner MA,Bax R,Allegaert K

    更新日期:2015-07-01 00:00:00

  • Impact of physiological, physicochemical and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavailability of rats and humans.

    abstract::The onset, intensity and duration of therapeutic response to a compound depend on the intrinsic pharmacological activity of the drug and pharmacokinetic factors related to its absorption, distribution, metabolism and elimination that are inherent to the biological system. The process of drug transfer from the site of ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425225.3.4.469

    authors: Hurst S,Loi CM,Brodfuehrer J,El-Kattan A

    更新日期:2007-08-01 00:00:00

  • Mathematical modeling of tumor growth and tumor growth inhibition in oncology drug development.

    abstract:INTRODUCTION:Approaches aiming to model the time course of tumor growth and tumor growth inhibition following a therapeutic intervention have recently been proposed for supporting decision making in oncology drug development. When considered in a comprehensive model-based approach, tumor growth can be included in the c...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2012.693480

    authors: Bernard A,Kimko H,Mital D,Poggesi I

    更新日期:2012-09-01 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

  • Role of cytidine deaminase in toxicity and efficacy of nucleosidic analogs.

    abstract:INTRODUCTION:Nucleosidic analogs such as pyrimidine and purine derivatives are mainstay in the field of treating cancers, both in adults and in children. All these drugs act as antimetabolite compounds, that is, they interfere with the ability of cancer cells to synthesize the nucleosides or the nucleotides necessary f...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2015.985648

    authors: Serdjebi C,Milano G,Ciccolini J

    更新日期:2015-05-01 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

  • Extended release, 6-month formulations of leuprolide acetate for the treatment of advanced prostate cancer: achieving testosterone levels below 20 ng/dl.

    abstract:INTRODUCTION:Luteinizing hormone-releasing hormone agonists such as leuprolide acetate (LA) are the most frequently utilized treatment of advanced prostate cancer as the regimen for achieving androgen deprivation therapy (ADT). The efficacy of LA is determined by extent of testosterone (T) suppression in prostate cance...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2015.1073711

    authors: Crawford ED,Moul JW,Sartor O,Shore ND

    更新日期:2015-01-01 00:00:00

  • Ezetimibe: an update on the mechanism of action, pharmacokinetics and recent clinical trials.

    abstract::Elevated serum cholesterol is a known risk factor for the development of coronary artery disease. Circulating cholesterol is a product of both cholesterol absorption from the gut and cellular cholesterol production. Ezetimibe is a novel cholesterol-lowering drug that acts at the brush border of the small intestine. Re...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.3.3.441

    authors: Sweeney ME,Johnson RR

    更新日期:2007-06-01 00:00:00

  • Everolimus: an update on the mechanism of action, pharmacokinetics and recent clinical trials.

    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

    authors: Sánchez-Fructuoso AI

    更新日期:2008-06-01 00:00:00

  • Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions.

    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

    authors: Sullivan A,Watkinson J,Waddington J,Park BK,Naisbitt DJ

    更新日期:2018-03-01 00:00:00

  • Pharmacoepigenetics: an element of personalized therapy?

    abstract:INTRODUCTION:Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2017.1260546

    authors: Majchrzak-Celińska A,Baer-Dubowska W

    更新日期:2017-04-01 00:00:00

  • Systems biology and functional genomics approaches for the identification of cellular responses to drug toxicity.

    abstract::Extensive growth in the field of molecular biology in recent decades has led to the development of new and powerful experimental and computational tools that enable the analysis of complex biological responses to chemical exposure on both a functional and structural genetic level. The ability to profile global respons...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.4.11.1379

    authors: Harrill AH,Rusyn I

    更新日期:2008-11-01 00:00:00

  • Mechanistic biomarkers for cytotoxic acute kidney injury.

    abstract::Acute kidney injury is a common condition and is associated with a high mortality rate. It has been recognised that routinely used measures of renal function, such as levels of blood urea nitrogen and serum creatinine, increase significantly only after substantial kidney injury occurs and then with a time delay. Insen...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2.5.697

    authors: Vaidya VS,Bonventre JV

    更新日期:2006-10-01 00:00:00

  • Old problem, new solutions: biomarker discovery for acetaminophen liver toxicity.

    abstract::Introduction: Although the hepatotoxicity of acetaminophen is a well-known problem, the search for reliable biomarker of toxicity is still a current issue as clinical tools are missing to assess patients intoxicated following chronic use, sequential ingestion, use of modified release formulations or in case of delayed...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2019.1642323

    authors: Gloor Y,Schvartz D,F Samer C

    更新日期:2019-08-01 00:00:00

  • In silico models for genotoxicity and drug regulation.

    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

    authors: Benigni R,Bassan A,Pavan M

    更新日期:2020-08-01 00:00:00

  • Alleviation of pain in painful diabetic neuropathy.

    abstract:INTRODUCTION:Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain management treatment is currently available. AREAS COVERED:The origin of PDN is enigmatic, and t...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1080/17425255.2016.1184648

    authors: Tajti J,Szok D,Majláth Z,Csáti A,Petrovics-Balog A,Vécsei L

    更新日期:2016-07-01 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

  • Mathematical models for dermal drug absorption.

    abstract:INTRODUCTION:Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approache...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2015.1063615

    authors: Selzer D,Neumann D,Schaefer UF

    更新日期:2015-01-01 00:00:00

  • Clinical implications of chemotherapy-induced tumor gene expression in human breast cancers.

    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

    authors: Tan SH,Lee SC

    更新日期:2010-03-01 00:00:00

  • Bioequivalence study of two formulations of itraconazole 100 mg capsules in healthy volunteers under fed conditions: a randomized, three-period, reference-replicated, crossover study.

    abstract:BACKGROUND:The aim of the study was to evaluate the bioequivalence of two itraconazole 100 mg capsule formulations. RESEARCH DESIGN AND METHODS:The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each stud...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1080/17425255.2018.1503649

    authors: Dragojević-Simić V,Kovačević A,Jaćević V,Rančić N,Djordjević S,Kilibarda V,Mikov M,Bokonjić D

    更新日期:2018-09-01 00:00:00

  • Advances in the development and use of human tissue-based techniques for drug toxicity testing.

    abstract:INTRODUCTION:Unacceptable failure rates in clinical trials are largely responsible for the high costs of bringing successful drugs to market - costs that are passed on to patients, insurers or healthcare providers. Furthermore, failures in clinical trials deny patients much-needed new drugs and potentially expose them ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.802770

    authors: Clotworthy M,Archibald K

    更新日期:2013-09-01 00:00:00

  • Zebrafish for drug toxicity screening: bridging the in vitro cell-based models and in vivo mammalian models.

    abstract:INTRODUCTION:Over the past decade, zebrafish have been tasked to play important roles from modeling human diseases to finding cures for them. Inadvertently, these fish now find themselves swimming along the drug development pipeline. A number of studies have been conducted to see if these small fish are up to the task ...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2011.562197

    authors: Sukardi H,Chng HT,Chan EC,Gong Z,Lam SH

    更新日期:2011-05-01 00:00:00

  • The role of afatinib in the management of non-small cell lung carcinoma.

    abstract:INTRODUCTION:Despite initial patient benefit, drug resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) is inevitable. One of the key mechanisms responsible for the development of acquired drug resistance is the secondary T790M missense mutation in exon 20 of the EGFR kinase domain. Afatinib is an ATP-...

    journal_title:Expert opinion on drug metabolism & toxicology

    pub_type: 杂志文章,评审

    doi:10.1517/17425255.2013.832755

    authors: Yap TA,Popat S

    更新日期:2013-11-01 00:00:00