4,066 results match your criteria Expert Opinion on Drug Metabolism & Toxicology[Journal]


Pharmacokinetics of monoamine oxidase B inhibitors in Parkinson's disease: current status.

Expert Opin Drug Metab Toxicol 2019 Apr 24:1-7. Epub 2019 Apr 24.

a Department of Neurology , St. Joseph Hospital Berlin-Weißensee , Berlin , Germany.

Introduction: Brain function depends considerably on the neurotransmission of biogenic monoamines. Their metabolism employs monoamine oxidase-B in neuronal and glial cells. Inhibition of monoamine oxidase-B elevates biogenic amine levels. Read More

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http://dx.doi.org/10.1080/17425255.2019.1607292DOI Listing

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen.

Expert Rev Clin Pharmacol 2019 Apr 22. Epub 2019 Apr 22.

a Leiden Network for Personalised Therapeutics , Leiden University Medical Center , Leiden , The Netherlands.

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30-100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride, has been successfully evaluated. Read More

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https://www.tandfonline.com/doi/full/10.1080/17512433.2019.1
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http://dx.doi.org/10.1080/17512433.2019.1610390DOI Listing
April 2019
1 Read

Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss.

Expert Opin Pharmacother 2019 Apr 8:1-12. Epub 2019 Apr 8.

c Academic Orthopaedic Unit , Aristotle University Medical School, Papageorgiou General Hospital , Thessaloniki , Greece.

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies. Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of-the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects. Read More

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https://www.tandfonline.com/doi/full/10.1080/14656566.2019.1
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http://dx.doi.org/10.1080/14656566.2019.1594772DOI Listing
April 2019
6 Reads

Safety, Tolerability, and Management of Toxic Effects of Phosphatidylinositol 3-Kinase Inhibitor Treatment in Patients With Cancer: A Review.

JAMA Oncol 2019 Mar 28. Epub 2019 Mar 28.

Division of Early Drug Development for Innovative Therapies, IEO, European Institute of Oncology, IRCCS Milano, Milan, Italy.

Importance: The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, which regulates multiple cellular processes, including metabolism, proliferation, motility, growth, and survival, is one of the most frequently dysregulated pathways in human cancers. The PI3K/AKT/mTOR cascade can be aberrantly activated by multiple factors, including diverse oncogenic genomic alterations in PIK3CA, PIK3R1, PTEN, AKT, TSC1, TSC2, LKB1, MTOR, and other critical genes, which can be used as targets for anticancer therapy. Limited single-agent activity, high levels of toxic effects, and a lack of predictive biomarkers for treatment selection have all been major barriers to the clinical development of these compounds. Read More

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http://dx.doi.org/10.1001/jamaoncol.2019.0034DOI Listing

Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors: an updated patent review (2016-2018).

Expert Opin Ther Pat 2019 Apr 29;29(4):243-259. Epub 2019 Mar 29.

a Merck Sharp & Dohme Corp , a subsidiary of Merck & Co., Inc , Kenilworth , NJ , USA.

Introduction: Interleukin-1 receptor-associated kinase 4 (IRAK4) is the most upstream kinase in Toll/Interleukin-1 receptor (TIR) signaling. Human and rodent genetics support the role of IRAK4 in immune function and the involvement of IRAK4-dependent signaling in certain cancers is hypothesized. The accumulating evidence has motivated the discovery of IRAK4 inhibitors that could be used therapeutically. Read More

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http://dx.doi.org/10.1080/13543776.2019.1597850DOI Listing

The role of pharmacogenomics in adverse drug reactions.

Expert Rev Clin Pharmacol 2019 Mar 27:1-36. Epub 2019 Mar 27.

a EuroEspes Biomedical Research Center , Institute of Medical Science and Genomic Medicine , Corunna , Spain.

Introduction: Adverse drug reactions (ADRs) are a major health concern worldwide. There are multiple causes of ADRs, some of which are preventable. Pharmacogenomics accounts for ≈80% variability in drug efficacy and safety. Read More

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http://dx.doi.org/10.1080/17512433.2019.1597706DOI Listing
March 2019
1 Read

A patent update on PDK1 inhibitors (2015-present).

Expert Opin Ther Pat 2019 Apr 29;29(4):271-282. Epub 2019 Mar 29.

a Department of Pharmacy , University of Pisa , Pisa , Italy.

Introduction: 3-Phosphoinositide-dependent kinase 1 (PDK1), the 'master kinase of the AGC protein kinase family', plays a key role in cancer development and progression. Although it has been rather overlooked, in the last decades a growing number of molecules have been developed to effectively modulate the PDK1 enzyme. Areas covered: This review collects different PDK1 inhibitors patented from October 2014 to December 2018. Read More

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http://dx.doi.org/10.1080/13543776.2019.1597852DOI Listing
April 2019
1 Read

Key insights from therapeutic drug monitoring in Crohn's disease patients.

Expert Opin Drug Metab Toxicol 2019 Mar 20:1-8. Epub 2019 Mar 20.

a Department of Gastroenterology and Hepatology, Amsterdam UMC , Vrije Universiteit Amsterdam , Amsterdam , The Netherlands.

Introduction: The incidence and prevalence of Crohn's disease are increasing causing a significant disease burden. Therapeutic drug monitoring (TDM) is advocated as a promising tool for personalized or individual-tailored therapy strategies and has been welcomed as a new means to improve current therapy strategies. Nevertheless, pharmacokinetic-based TDM has limitations, and straightforward target concentrations for most therapies are lacking. Read More

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http://dx.doi.org/10.1080/17425255.2019.1597054DOI Listing

A patent update on cannabinoid receptor 1 antagonists (2015-2018).

Expert Opin Ther Pat 2019 Apr 8;29(4):261-269. Epub 2019 Apr 8.

a Center for Drug Discovery , RTI International , RTP , NC , USA.

Introduction: The endocannabinoid system is an important regulator of various physiological processes. Preclinical and clinical studies indicate that attenuation of the endocannabinoid system via antagonism of the type 1 cannabinoid receptor (CB1) is an excellent strategy to treat obesity, metabolic syndrome and associated disorders. However, centrally acting antagonists of CB1 also produce adverse effects like depression and anxiety. Read More

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http://dx.doi.org/10.1080/13543776.2019.1597851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476312PMC
April 2019
2 Reads

Bruton's tyrosine kinase (BTK) inhibitors in treating cancer: a patent review (2010-2018).

Expert Opin Ther Pat 2019 Apr;29(4):217-241

a Department of Medicinal Chemistry, School of Pharmacy, Health Science Center , Xi'an Jiaotong University , Xi'an , Shaanxi P.R. China.

Introduction: Bruton's tyrosine kinase (BTK) plays a critical role in the regulation of survival, proliferation, activation and differentiation of B-lineage cells. It participates by regulating multiple cellular signaling pathways, including B cell receptor and FcR signaling cascades. BTK is abundantly expressed and constitutively active in the pathogenesis of B cell hematological malignancies, as well as several autoimmune diseases. Read More

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http://dx.doi.org/10.1080/13543776.2019.1594777DOI Listing
April 2019
2 Reads

Pharmacokinetic and pharmacodynamic considerations in the treatment of the elderly patient with hypertension.

Expert Opin Drug Metab Toxicol 2019 Apr 16;15(4):287-297. Epub 2019 Mar 16.

b Department of Internal Medicine , Erasmus MC, University Medical Center Rotterdam , Rotterdam , The Netherlands.

Introduction: Hypertension is an important risk factor for developing cardiovascular diseases. It is more prevalent in the elderly population. Recently updated American and European guidelines recommend treating every elderly patient with hypertension independent of age, starting with a low dose of antihypertensive drugs. Read More

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http://dx.doi.org/10.1080/17425255.2019.1588249DOI Listing
April 2019
1 Read

RX-3117 (fluorocyclopentenyl cytosine): a novel specific antimetabolite for selective cancer treatment.

Expert Opin Investig Drugs 2019 Apr 16;28(4):311-322. Epub 2019 Mar 16.

a Department of Medical Oncology , Amsterdam UMC, VU University Medical Center , Amsterdam , Netherlands.

Introduction: RX-3117 is an oral, small molecule cytidine analog anticancer agent with an improved pharmacological profile relative to gemcitabine and other nucleoside analogs. The agent has excellent activity against various cancer cell lines and xenografts including gemcitabine-resistant variants and it has excellent oral bioavailability; it is not a substrate for the degradation enzyme cytidine deaminase. RX-3117 is being evaluated at a daily oral schedule of 700 mg (5 days/week for 3 weeks) which results in plasma levels in the micromolar range that have been shown to be cytotoxic to cancer cells. Read More

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http://dx.doi.org/10.1080/13543784.2019.1583742DOI Listing

ABCG2/BCRP: variants, transporter interaction profile of substrates and inhibitors.

Expert Opin Drug Metab Toxicol 2019 Apr 16;15(4):313-328. Epub 2019 Mar 16.

a SOLVO Biotechnology , Szeged , Hungary.

Introduction: ABCG2 has a broad substrate specificity and is one of the most important efflux proteins modulating pharmacokinetics of drugs, nutrients and toxicokinetics of toxicants. ABCG2 is an important player in transporter-mediated drug-drug interactions (tDDI). Areas covered: The aims of the review are i) to cover transporter interaction profile of substrates and inhibitors that can be utilized to test interaction of drug candidates with ABCG2, ii) to highlight main characteristics of in vitro testing and iii) to describe the structural basis of the broad substrate specificity of the protein. Read More

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http://dx.doi.org/10.1080/17425255.2019.1591373DOI Listing

Metabolism and inflammation: implications for traumatic brain injury therapeutics.

Expert Rev Neurother 2019 Mar 8;19(3):227-242. Epub 2019 Mar 8.

a Division of Neurosurgery, Department of Clinical Neurosciences , University of Cambridge , Cambridge , UK.

Introduction: Traumatic Brain Injury (TBI) is a leading cause of death and disability in young people, affecting 69 million people annually, worldwide. The initial trauma disrupts brain homeostasis resulting in metabolic dysfunction and an inflammatory cascade, which can then promote further neurodegenerative effects for months or years, as a 'secondary' injury. Effective targeting of the cerebral inflammatory system is challenging due to its complex, pleiotropic nature. Read More

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https://www.tandfonline.com/doi/full/10.1080/14737175.2019.1
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http://dx.doi.org/10.1080/14737175.2019.1582332DOI Listing
March 2019
4 Reads

Using DPP-4 inhibitors to modulate beta cell function in type 1 diabetes and in the treatment of diabetic kidney disease.

Expert Opin Investig Drugs 2019 Apr 19;28(4):377-388. Epub 2019 Mar 19.

Introduction: DPP-4 inhibitors have pleomorphic effects that extend beyond the anti-hyperglycemic labeled use of the drug. DPP-4 inhibitors have demonstrated promising renal protective effects in T2DM and T1DM and protective effects against immune destruction of pancreatic beta-cells in T1DM. Areas covered: The efficacy of DPP-4 inhibitors in the treatment of diabetic kidney disease and possible adjunct with insulin in the treatment of T1DM to preserve beta-cell function. Read More

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http://dx.doi.org/10.1080/13543784.2019.1592156DOI Listing
April 2019
2 Reads

Emerging drugs for the treatment of hypercholesterolemia.

Expert Opin Emerg Drugs 2019 03 21;24(1):63-69. Epub 2019 Mar 21.

a Medical and Surgical Sciences Department , University of Bologna , Bologna , Italy.

Introduction: Despite the consolidated role of statins and ezetimibe to treat hypercholesterolemia, often the desirable low-density lipoprotein cholesterol (LDL-C) values are not achieved, with a consequent increase of the residual cardiovascular (CV) risk. Areas covered: In this review, we summarize the main pharmacological characteristics of new lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, cholesteryl ester transfer protein inhibitors, microsomal triglyceride transfer protein inhibitors, ATP citrate lyase inhibitors, antisense oligonucleotides, small interfering RNA, and peroxisome proliferator-activated receptors type α agonists. The available clinical evidence of efficacy and safety as well as the prospects of application, based on the different mechanisms and targets of action, is critically discussed. Read More

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http://dx.doi.org/10.1080/14728214.2019.1591372DOI Listing
March 2019
1 Read

A therapeutic patent overview of MDM2/X-targeted therapies (2014-2018).

Expert Opin Ther Pat 2019 Mar 1;29(3):151-170. Epub 2019 Mar 1.

a Department of Organic Chemistry, Faculty of Chemistry , Jagiellonian University , Krakow , Poland.

Introduction: MDM2 and MDMX proteins provide the inhibition of p53 tumor suppressor, thus allowing for accelerated mutation-driven cancer microevolution. A pharmacological blockade of MDM2/X-p53 interaction results in p53 reactivation in p53 cells, leading to cancer growth inhibition. Throughout the past 20 years, multiple chemical entities have been proposed to reactivate p53 by antagonizing MDM2/X proteins. Read More

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http://dx.doi.org/10.1080/13543776.2019.1582645DOI Listing
March 2019
3 Reads

Metabolism of the failing heart and the impact of SGLT2 inhibitors.

Expert Opin Drug Metab Toxicol 2019 Apr 11;15(4):275-285. Epub 2019 Mar 11.

a Atherothrombosis Research Unit, Mount Sinai Heart , Icahn School of Medicine at Mount Sinai , New York , USA.

Introduction: Cardiac metabolism represents a complex network of numerous pathways responsible for an adequate supply of ATP to the incessant contractile apparatus. Impairments of such pathways are associated with myocardial dysfunction. The newest antidiabetic drugs, the SGLT2 inhibitors, have been demonstrated to reduce cardiovascular mortality and heart failure hospitalizations. Read More

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https://www.tandfonline.com/doi/full/10.1080/17425255.2019.1
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http://dx.doi.org/10.1080/17425255.2019.1588886DOI Listing
April 2019
8 Reads

Estrogen sulfotransferase in the metabolism of estrogenic drugs and in the pathogenesis of diseases.

Expert Opin Drug Metab Toxicol 2019 Apr 18;15(4):329-339. Epub 2019 Mar 18.

a Center for Pharmacogenetics and Department of Pharmaceutical Sciences , University of Pittsburgh , Pittsburgh , PA , USA.

Introduction: Biotransformation is important in the metabolism of endobiotics and xenobiotics. This process comprises the activity of phase I and phase II enzymes. Estrogen sulfotransferase (SULT1E1 or EST) is a phase II conjugating enzyme that belongs to the family of cytosolic sulfotransferases. Read More

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http://dx.doi.org/10.1080/17425255.2019.1588884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428602PMC
April 2019
3 Reads

Pharmacokinetics of serotonergic drugs: focus on OCD.

Expert Opin Drug Metab Toxicol 2019 Apr 8;15(4):261-273. Epub 2019 Mar 8.

a Dipartimento di Medicina Clinica e Sperimentale, Section of Psychiatry , University of Pisa , Pisa , Italy.

Introduction: Although the treatment of obsessive-compulsive disorder (OCD), a common, chronic, and disabling psychiatric condition, has significantly improved in the last decades, with the demonstration of the specific effectiveness of serotonin reuptake inhibitors (SRIs), a large proportion of patients still show high relapse rates. In addition, pharmacological treatments should be maintained for years, so that the clinicians should take into account the pharmacokinetic changes in the long-term, which may be responsible for dangerous side effects or interactions. Areas covered: The aim of this paper was to review the literature on the pharmacokinetics of SSRIs and clomipramine, and on their pharmacokinetic parameters in OCD patients. Read More

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http://dx.doi.org/10.1080/17425255.2019.1584611DOI Listing
April 2019
1 Read

A patent update on therapeutic applications of urease inhibitors (2012-2018).

Expert Opin Ther Pat 2019 Mar 6;29(3):181-189. Epub 2019 Mar 6.

a H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences , University of Karachi , Karachi , Pakistan.

Introduction: Urease is a nickel-containing metalloenzyme that is commonly found in different bacteria, plants, algae, and fungi and mediates the growth of many pathogenic bacteria in the acidic environment of the stomach. Despite the large number of molecules known to have excellent urease inhibitory activity, there is an alarming lack of urease inhibitor drugs on the market. Area covered: This review aims to provide a comprehensive overview of the different types of molecules patented as potent urease inhibitors from the year 2012 to 2018. Read More

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http://dx.doi.org/10.1080/13543776.2019.1584612DOI Listing
March 2019
1 Read
4.297 Impact Factor

Therapy of acute myeloid leukemia: therapeutic targeting of tyrosine kinases.

Expert Opin Investig Drugs 2019 Apr 27;28(4):337-349. Epub 2019 Feb 27.

a Department of Medicine , Penn State Hershey Medical Center , Hershey , PA , USA.

Introduction: Tyrosine kinases (TKs) drive cell survival and proliferation in many normal and malignant cell types. TKs are frequently mutated in acute myeloid leukemia (AML) and hence are increasingly targeted. The management of AML has dramatically improved because of TKI-targeted treatment. Read More

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http://dx.doi.org/10.1080/13543784.2019.1584610DOI Listing

Cannabis, a potential treatment option in pediatric IBD? Still a long way to go.

Expert Rev Clin Pharmacol 2019 Apr 26;12(4):355-361. Epub 2019 Feb 26.

b Department of Paediatric Gastroenterology , Erasmus MC-Sophia Children's Hospital , Rotterdam , The Netherlands.

Introduction: The onset of inflammatory bowel disease (IBD) in children is rising. Current treatment options are based on immunomodulatory therapy. Alternative treatment options are upcoming since they appear to be effective in individual patients. Read More

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http://dx.doi.org/10.1080/17512433.2019.1582330DOI Listing
April 2019
3 Reads

Aldose reductase inhibitors: 2013-present.

Expert Opin Ther Pat 2019 Mar 27;29(3):199-213. Epub 2019 Feb 27.

a Dipartimento di Farmacia , Università di Pisa , Pisa , Italy.

Introduction: Aldose reductase (ALR2) is both the key enzyme of the polyol pathway, whose activation under hyperglycemic conditions leads to the development of chronic diabetic complications, and the crucial promoter of inflammatory and cytotoxic conditions, even under a normoglycemic status. Accordingly, it represents an excellent drug target and a huge effort is being done to disclose novel compounds able to inhibit it. Areas covered: This literature survey summarizes patents and patent applications published over the last 5 years and filed for natural, semi-synthetic and synthetic ALR2 inhibitors. Read More

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http://dx.doi.org/10.1080/13543776.2019.1582646DOI Listing

Emerging patient-specific treatment modalities in head and neck cancer - a systematic review.

Expert Opin Investig Drugs 2019 Apr 26;28(4):365-376. Epub 2019 Feb 26.

b Department of Radiation Oncology , University of Lausanne, Centre Hospitalier Universitaire Vaudois (CHUV) , Lausanne , Switzerland.

Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates heterogeneous molecular characteristics and features of tumor-host interaction. Beside radiotherapy and surgery, the current standard of care in systemic treatment involves the use of cytotoxic chemotherapy, monoclonal antibodies (mAbs), and tyrosine kinase inhibitors (TKIs). There are also other modalities being developed under the category of immunotherapy, but they are overshadowed by the recent advancements of immune checkpoint inhibitors. Read More

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http://dx.doi.org/10.1080/13543784.2019.1582642DOI Listing
April 2019
3 Reads

Investigational multitargeted kinase inhibitors in development for head and neck neoplasms.

Expert Opin Investig Drugs 2019 Apr 26;28(4):351-363. Epub 2019 Feb 26.

a Department of Otolaryngology - Head and Neck Surgery , University of California , San Francisco , CA , USA.

Introduction: Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) survival rates remain stagnant. Current treatment is associated with significant toxicities and includes chemotherapy, radiation, surgery, and few targeted treatments. Targeted treatments, epidermal growth factor receptor (EGFR)-targeted agent, cetuximab, and immune checkpoint inhibitors, pembrolizumab and nivolumab, show improved toxicity profiles and modestly improved survival in select patients. Read More

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http://dx.doi.org/10.1080/13543784.2019.1581172DOI Listing
April 2019
1 Read

Experimental therapies targeting apolipoprotein C-III for the treatment of hyperlipidemia - spotlight on volanesorsen.

Expert Opin Investig Drugs 2019 Apr 15;28(4):389-394. Epub 2019 Feb 15.

a First Propedeutic Department of Internal Medicine, Medical School , Aristotle University of Thessaloniki, AHEPA Hospital , Thessaloniki , Greece.

Introduction: Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides (TG). Apolipoprotein C3 (APOC3) is a key regulator of TG metabolism and its targeting may reduce TG levels and cardiovascular risk. Read More

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http://dx.doi.org/10.1080/13543784.2019.1582028DOI Listing
April 2019
1 Read

The efficacy and safety of exenatide once weekly in patients with type 2 diabetes.

Expert Opin Pharmacother 2019 Apr 7;20(5):501-510. Epub 2019 Feb 7.

a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark.

Introduction: Exenatide once weekly (QW) is a glucagon-like peptide 1 receptor agonist (GLP-1RA) that was approved in 2012 in Europe and the U.S.A. Read More

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http://dx.doi.org/10.1080/14656566.2019.1571040DOI Listing
April 2019
1 Read

An evaluation of roflumilast and PDE4 inhibitors with a focus on the treatment of asthma.

Expert Opin Pharmacother 2019 Apr 5;20(5):609-620. Epub 2019 Feb 5.

a Department of Medicine , McMaster University , Hamilton , ON , Canada.

Introduction: Asthma is a common chronic airway inflammatory disease characterized by diverse inflammatory events leading to airway hyperresponsiveness and reversible airflow obstruction. Corticosteroids have been the mainstay for asthma treatment due to their broad anti-inflammatory actions; however, other medications such as phosphodiesterase 4 inhibitors also demonstrate anti-inflammatory activity in the airways. Areas covered: This review describes tissue expression of phosphodiesterase 4 in the airways, the different phosphodiesterase 4 isoenzymes identified, and the anti-inflammatory activities of phosphodiesterase 4 inhibition in asthma and related findings in chronic obstructive pulmonary disease (COPD). Read More

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https://www.tandfonline.com/doi/full/10.1080/14656566.2019.1
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http://dx.doi.org/10.1080/14656566.2019.1570132DOI Listing
April 2019
14 Reads

Enhancement of lung levels of antibiotics by ambroxol and bromhexine.

Expert Opin Drug Metab Toxicol 2019 Mar 7;15(3):213-218. Epub 2019 Feb 7.

b Department of Pharmaceutical Sciences, College of Pharmacy , University of New Mexico Health Sciences Center , Albuquerque , NM , USA.

Introduction: Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to optimize therapy using existing agents are also attractive. Ambroxol induces lung autophagy at human-relevant doses and improves lung levels of several approved antibiotics. Read More

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http://dx.doi.org/10.1080/17425255.2019.1578748DOI Listing
March 2019
4 Reads

Pharmacokinetics and pharmacodynamics of new acute treatments for migraine.

Expert Opin Drug Metab Toxicol 2019 Mar 12;15(3):189-198. Epub 2019 Feb 12.

d Regional Referral Headache Centre, Sant'Andrea Hospital, Department of Clinical and Molecular Medicine , Sapienza University of Rome , Rome , Italy.

Introduction: Recommended medications for the acute treatment of migraine encompass triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), and analgesics. While it is true that triptans have been the first successful mechanism-driven treatment in the field, recently, new targets involved in migraine pathogenesis have emerged and new drug classes have been studied for migraine attack therapy. Areas covered: Pharmacodynamics and pharmacokinetics of the new acute treatments of migraine (i. Read More

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https://www.tandfonline.com/doi/full/10.1080/17425255.2019.1
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http://dx.doi.org/10.1080/17425255.2019.1578749DOI Listing
March 2019
13 Reads

Drug-drug interactions of a two-drug regimen of dolutegravir and lamivudine for HIV treatment.

Expert Opin Drug Metab Toxicol 2019 Mar 11;15(3):245-252. Epub 2019 Feb 11.

b Department of Infectious Diseases , ASST Fatebenefratelli Sacco University Hospital , Milan , Italy.

Introduction: The GEMINI trials have recently shown that a two-drug regimen of dolutegravir plus lamivudine was non-inferior to a three-drug regimen in HIV-infected naïve patients. Accordingly, it is important that physicians be aware and confident about the drug-drug interactions (DDIs) involving dolutegravir, lamivudine, and other medications. Areas covered: Here, we firstly update the available information on the pharmacokinetic features of dolutegravir and lamivudine; subsequently, the articles mainly deals with the predictable DDIs for both antiretroviral drugs, attempting to underline their clinical implications. Read More

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http://dx.doi.org/10.1080/17425255.2019.1577821DOI Listing
March 2019
1 Read

Rational and clinical development of the anti-MAdCAM monoclonal antibody for the treatment of IBD.

Expert Opin Biol Ther 2019 Apr 11;19(4):361-366. Epub 2019 Feb 11.

a Inflammatory Bowel Disease Center and Amsterdam Gastroenterology and Metabolism , Amsterdam UMC, University of Amsterdam , Amsterdam , The Netherlands.

Introduction: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in gut-associated lymphoid tissue is upregulated in patients with inflammatory bowel disease (IBD). Blocking adhesion molecules and thereby inhibiting migration of lymphocytes into sites of inflammation in the gut is an attractive new treatment target in drug development for IBD. Areas covered: This review discusses the preclinical and clinical experience on SHP647 (previously called PF-00547659 and PF-00547,659), a fully human IgG2K monoclonal antibody that binds to MAdCAM-1 to selectively reduce lymphocyte homing to the intestinal tract. Read More

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http://dx.doi.org/10.1080/14712598.2019.1576631DOI Listing
April 2019
2 Reads

Pharmacokinetic considerations for anti-epileptic drugs in children.

Expert Opin Drug Metab Toxicol 2019 Mar 7;15(3):199-211. Epub 2019 Feb 7.

a Department of Pediatrics , University of L'Aquila , L'Aquila , Italy.

Introduction: Epilepsy is a chronic and debilitating neurological disease, with a peak of incidence in the first years of life. Today, the vast armamentarium of antiepileptic drugs (AEDs) available make even more challenging to select the most appropriate AED and establish the most effective dosing regimen. In fact, AEDs pharmacokinetics is under the influence of important age-related factors which cannot be ignored. Read More

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https://www.tandfonline.com/doi/full/10.1080/17425255.2019.1
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http://dx.doi.org/10.1080/17425255.2019.1575361DOI Listing
March 2019
8 Reads

ATP-competitive DNA gyrase and topoisomerase IV inhibitors as antibacterial agents.

Expert Opin Ther Pat 2019 Mar 6;29(3):171-180. Epub 2019 Feb 6.

a Faculty of Pharmacy , University of Ljubljana , Ljubljana , Slovenia.

Introduction: The bacterial topoisomerases DNA gyrase and topoisomerase IV are validated targets for development of novel antibacterial agents. Fluoroquinolones inhibit the catalytic GyrA and/or ParC(GrlA) subunit and have been commonly used, although these have toxicity liabilities that restrict their use. The ATPase GyrB and ParE(GrlB) subunits have been much less explored and after withdrawal of novobiocin, there are no further marketed inhibitors . Read More

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http://dx.doi.org/10.1080/13543776.2019.1575362DOI Listing
March 2019
2 Reads

Safety of recombinant coagulation factors in treating hemophilia.

Expert Opin Drug Saf 2019 Feb 22;18(2):75-85. Epub 2019 Feb 22.

b Department of Hematology , University of Florence , Italy.

Introduction: During the last decade, new FVIII/IX concentrates have been developed for the treatment of patients affected by hemophilia A/B. Significant progress has been achieved regarding their half-life, but the old issue of immunogenicity and new concerns about safety need to be addressed. Areas covered: After the implementation of virucidal methods, both plasma-derived and recombinant clotting factor concentrates achieved a very safe profile. Read More

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http://dx.doi.org/10.1080/14740338.2019.1574743DOI Listing
February 2019

Experimental and investigational phosphodiesterase inhibitors in development for asthma.

Expert Opin Investig Drugs 2019 Mar 24;28(3):261-266. Epub 2019 Jan 24.

c 5th Pulmonary Department , "Sotiria" Chest Diseases Hospital , Athens , Greece.

Introduction: Severe, inadequately-controlled asthma remains a clinical challenge. For this reason, clinical trials and preclinical experimental studies on novel agents as an add-on therapies continue emerge. Phosphodiesterases (PDEs) are enzymes that regulate the function of immune cells by hydrolyzing cyclic guanosine monophosphate/cGMP and cyclic adenosine monophosphate/cAMP. Read More

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https://www.tandfonline.com/doi/full/10.1080/13543784.2019.1
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http://dx.doi.org/10.1080/13543784.2019.1571582DOI Listing
March 2019
7 Reads

Strategies to optimize drug half-life in lead candidate identification.

Expert Opin Drug Discov 2019 Mar 24;14(3):221-230. Epub 2019 Jan 24.

a Department of Drug Metabolism and Pharmacokinetics , Genentech , South San Francisco , CA , USA.

Introduction: The PK optimization of drug candidates is one of the most resource-intensive tasks in pharmaceutical research and development. With the increasing availability of in silico, in vitro and mechanistic in vivo ADME models, drug discovery scientists have progressively learned to recognize common SAR patterns and engineer data-driven strategies to accelerate the resolution of ADME issues in lead optimization. Many of these strategies gravitate toward the concept of drug-likeness, which defines a number of optimal holistic physicochemical parameters (such as lipophilicity) that idealized oral drugs possess. Read More

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http://dx.doi.org/10.1080/17460441.2019.1569625DOI Listing
March 2019
3 Reads

Capecitabine for the treatment of pancreatic cancer.

Expert Opin Pharmacother 2019 Mar 16;20(4):399-409. Epub 2019 Jan 16.

a Division of Hematology/Oncology , Tufts Medical Center - Tufts University School of Medicine , Boston , MA , USA.

Introduction: Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) which is converted to 5FU by a series of reactions catalyzed by different enzymes, the last of the enzymes being thymidine phosphorylase (TP). TP is found to be elevated in tumor cells in comparison to normal cells, which consequently tumor-localizes the production of 5-FU, thereby limiting its systemic toxicity. Today, capecitabine is extensively used for the treatment of many solid malignancies, with a particular focus in breast and gastrointestinal tumors, but also in pancreatic cancer. Read More

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http://dx.doi.org/10.1080/14656566.2018.1560422DOI Listing
March 2019
1 Read
3.534 Impact Factor

Chemical activation of estrogen and aryl hydrocarbon receptor signaling pathways and their interaction in toxicology and metabolism.

Expert Opin Drug Metab Toxicol 2019 Mar 27;15(3):219-229. Epub 2019 Jan 27.

a Department of Chemical & Product Safety , German Federal Institute for Risk Assessment (BfR) , Berlin , Germany.

Introduction: Estrogen receptors (ERs) and the arylhydrocarbon receptor (AHR) are ligand-activated transcription factors that regulate the expression of genes involved in many physiological processes. With both receptors binding a broad range of natural and anthropogenic ligands, they are molecular targets for many substances, raising concerns for possible health effects. Areas covered: This review shall give a brief overview on the physiological functions of both receptors including their underlying molecular mechanisms. Read More

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https://www.tandfonline.com/doi/full/10.1080/17425255.2019.1
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http://dx.doi.org/10.1080/17425255.2019.1569627DOI Listing
March 2019
12 Reads

New drugs under investigation for the treatment of alopecias.

Expert Opin Investig Drugs 2019 Mar 22;28(3):275-284. Epub 2019 Jan 22.

b Department of Dermatology and Cutaneous Surgery , University of Miami Miller School of Medicine , Miami , FL , USA.

Introduction: Alopecia is a very common complaint in medical practice, which usually has a large psychological impact in patients. Treatment of alopecia is often difficult and frustrating for patients and clinicians owing to the slow growth rate of the hair, long treatment terms, limited efficacy, and possible adverse side effects. Areas covered: This paper reviews the new and emerging treatments for two of the most common forms of alopecia, known as androgenetic alopecia and alopecia areata. Read More

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http://dx.doi.org/10.1080/13543784.2019.1568989DOI Listing
March 2019
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GPR17 receptor modulators and their therapeutic implications: review of recent patents.

Expert Opin Ther Pat 2019 Feb 24;29(2):85-95. Epub 2019 Jan 24.

a School of Pharmacy, Medicinal Chemistry Unit , University of Camerino , Camerino , Italy.

Introduction: The GPR17 receptor, phylogenetically related to both purinergic P2Y and CysLT receptors, is mainly expressed in the CNS and, in general, in organs that can typically undergo ischemic damage. This receptor is involved in various pathologies including stroke, brain and spinal cord trauma, multiple sclerosis and in all diseases characterized by neuronal and myelin dysfunction. Therefore, there is a strong needed to identify molecules capable of binding specifically to GPR17 receptors. Read More

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http://dx.doi.org/10.1080/13543776.2019.1568990DOI Listing
February 2019
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A patent review of arginine methyltransferase inhibitors (2010-2018).

Expert Opin Ther Pat 2019 Feb;29(2):97-114

a CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Drug Discovery and Design Center , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China.

Introduction: Protein arginine methyltransferases (PRMTs) are fundamental enzymes that specifically modify the arginine residues of versatile substrates in cells. The aberrant expression and abnormal enzymatic activity of PRMTs are associated with many human diseases, especially cancer. PRMTs are emerging as promising drug targets in both academia and industry. Read More

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http://dx.doi.org/10.1080/13543776.2019.1567711DOI Listing
February 2019
12 Reads
4.297 Impact Factor

Pharmacokinetics and pharmacodynamics of monoclonal antibodies for asthma treatment.

Expert Opin Drug Metab Toxicol 2019 Feb 24;15(2):113-120. Epub 2019 Jan 24.

b Department of Internal Medicine, Respiratory Disease Clinic , IRCCS Humanitas Clinical and Research Center, Humanitas University , Milan , Italy.

Introduction: Asthma is a chronic inflammatory airway disease. It occurs in a 'severe' form in about 8-10% of asthmatic patients. In the last decade, the development of biological drugs (e. Read More

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https://www.tandfonline.com/doi/full/10.1080/17425255.2019.1
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http://dx.doi.org/10.1080/17425255.2019.1568409DOI Listing
February 2019
12 Reads

Novel β-lactam-β-lactamase inhibitor combinations: expectations for the treatment of carbapenem-resistant Gram-negative pathogens.

Expert Opin Drug Metab Toxicol 2019 Feb 10;15(2):133-149. Epub 2019 Jan 10.

a 1st Department of Internal Medicine-Infectious Diseases , Hygeia General Hospital , Athens , Greece.

Introduction: The burden of antimicrobial resistance among Gram-negative bacteria is increasing and growing into a major threat of public health. Treatment options for carbapenem-resistant Enterobacteriaceae are limited and resistance rates to existing compounds are mounting. The pipeline includes only a small number of novel anti-infective agents in development or in the market with promising results against multidrug-resistant (MDR) Gram-negative. Read More

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https://www.tandfonline.com/doi/full/10.1080/17425255.2019.1
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http://dx.doi.org/10.1080/17425255.2019.1563071DOI Listing
February 2019
3 Reads

Selective Tyk2 inhibitors as potential therapeutic agents: a patent review (2015-2018).

Expert Opin Ther Pat 2019 02 22;29(2):137-149. Epub 2019 Jan 22.

a Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University , Hangzhou , Zhejiang Province , China.

Introduction: Tyrosine kinase 2 (Tyk2) is a non-receptor tyrosine-protein kinase, an enzyme that in humans is encoded by the TYK2 gene. Tyk2, together with three other family subtypes, namely, Jak1, Jak2, and Jak3, belong to the JAK family. Before 2014, far more publications and patents appeared in public domain attributing to the development of selective Jak2 and Jak3 inhibitors than those for selective Tyk2 and Jak1 inhibitors. Read More

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https://www.tandfonline.com/doi/full/10.1080/13543776.2019.1
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http://dx.doi.org/10.1080/13543776.2019.1567713DOI Listing
February 2019
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Treating obesity in patients with cardiovascular disease: the pharmacotherapeutic options.

Expert Opin Pharmacother 2019 Apr 7;20(5):585-593. Epub 2019 Jan 7.

b Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medicine , Comprehensive Weight Control Center , New York , NY , USA.

Introduction: Obesity is a growing health problem that has numerous comorbidities, including cardiovascular disease (CVD). The multi-disciplinary treatment of obesity now includes the use of pharmacotherapy. When treating patients with obesity and CVD, certain medications may be more appropriate than others. Read More

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http://dx.doi.org/10.1080/14656566.2018.1561867DOI Listing
April 2019
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Pharmacotherapeutic strategies for treating pancreatic cancer: advances and challenges.

Expert Opin Pharmacother 2019 Apr 28;20(5):535-546. Epub 2018 Dec 28.

a Department of Oncology, Karmanos Cancer institute , Wayne State University , Detroit , MI , USA.

Introduction: Despite many efforts to improve the outcome of pancreatic ductal adenocarcinoma (PDAC), its prognosis remains poor, which is mostly related to late diagnosis and drug resistance. Improving systemic therapy is considered the major challenge in improving the outcome of this disease. Areas covered: This review covers novel chemotherapy and targeted agents in the treatment of PDAC, with a focus on advanced stage disease. Read More

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https://www.tandfonline.com/doi/full/10.1080/14656566.2018.1
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http://dx.doi.org/10.1080/14656566.2018.1561869DOI Listing
April 2019
11 Reads

Rapastinel - an investigational NMDA-R modulator for major depressive disorder: evidence to date.

Expert Opin Investig Drugs 2019 Feb 26;28(2):113-119. Epub 2018 Dec 26.

a Mood Disorders Psychopharmacology Unit , University Health Network , Toronto , Canada.

Introduction: Major depressive disorder (MDD) is a debilitating disorder with increasing prevalence globally. Despite the development of novel treatments for MDD, many patients present with treatment resistant depression (TRD), identified by treatment non-response following one or more adequate trials of an antidepressant. Rapastinel may prove to be a viable treatment for TRD; it has the potential to produce a rapid antidepressant response without serious adverse events and improve functional symptoms. Read More

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https://www.tandfonline.com/doi/full/10.1080/13543784.2019.1
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http://dx.doi.org/10.1080/13543784.2019.1559295DOI Listing
February 2019
19 Reads

An update on polyphenol disposition via coupled metabolic pathways.

Expert Opin Drug Metab Toxicol 2019 Feb 24;15(2):151-165. Epub 2018 Dec 24.

a Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine , Guangzhou University of Chinese Medicine , Guangzhou, Guangdong , China.

Introduction: Polyphenols, which are widely distributed in plants and the human diets, are known to have numerous biological activities. However, the low bioavailability of polyphenols is mediated by coupled metabolic pathways. Areas covered: The key role of the interplay between drug metabolic enzymes (DMEs) and efflux transporters (ETs), nuclear receptors (NRs), and intestinal microflora in the disposition of polyphenols is summarized. Read More

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http://dx.doi.org/10.1080/17425255.2019.1559815DOI Listing
February 2019