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Clinical Pharmacology and Therapeutics

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https://read.qxmd.com/read/30773619/past-present-and-future-of-drug-drug-interactions
#1
René H Levy, Isabelle Ragueneau-Majlessi
No abstract text is available yet for this article.
February 17, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30773618/research-projects-supported-by-the-university-of-california-san-francisco-stanford-center-of-excellence-in-regulatory-science-and-innovation
#2
Kathleen M Giacomini, Lawrence Lin, Russ B Altman
No abstract text is available yet for this article.
February 17, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30771252/drug-drug-interactions-of-infectious-disease-treatments-in-low-income-countries-a-neglected-topic
#3
Savannah J McFeely, Jingjing Yu, Ping Zhao, Susan Hershenson, Steven Kern, Isabelle Ragueneau-Majlessi, Dan Hartman
Despite recent advances in recognizing and reducing the risk of drug-drug interactions (DDIs) in developed countries, there are still significant challenges in managing DDIs in low income countries (LICs) worldwide. In the treatment of major infectious diseases in these regions, multiple factors contribute to ineffective management of DDIs that lead to loss of efficacy or increased risk of adverse events to patients. Some of these difficulties, however, can be overcome. This review aims to evaluate the inherent complexities of DDI management in LICs from pharmacological standpoints and illustrates the unique barriers to effective management of DDIs, such as the challenges of co-infection and treatment settings...
February 16, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30770546/bispecific-antibodies-in-the-treatment-of-hematologic-malignancies
#4
REVIEW
Johannes Duell, Philip E Lammers, Ivana Djuretic, Allison G Chunyk, Shilpa Alekar, Ira Jacobs, Saar Gill
Monoclonal antibody (mAb) therapies are an important approach for the treatment of hematologic malignancies, but typically show low single-agent activity. Bispecific antibodies, however, redirect immune cells to the tumor for subsequent lysis, and preclinical and accruing clinical data support single-agent efficacy of these agents in hematologic malignancies, presaging an exciting era in the development of novel bispecific formats. This review discusses recent developments in this area, highlighting the challenges in delivering effective immunotherapies for patients...
February 15, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30756383/probes-and-cocktails-for-drug-drug-interaction-evaluation-the-future-is-microdosing
#5
Gerd Mikus
No abstract text is available yet for this article.
February 12, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739326/can-innovation-in-regulatory-science-address-health-care-cost-burdens
#6
Gregory W Daniel, Morgan H Romine, Mark B McClellan
No abstract text is available yet for this article.
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739325/no-clinically-relevant-interactions-of-st-john-s-wort-extract-ze-117-low-in-hyperforin-with-cytochrome-p450-enzymes-and-p-glycoprotein
#7
Catherine Zahner, Esther Kruttschnitt, Julia Uricher, Michael Lissy, Martin Hirsch, Simon Nicolussi, Stephan Krähenbühl, Jürgen Drewe
Hypericum perforatum L. (St. John's wort) is used to treat mild-to-moderate depression. Its potential safety risks are pharmacokinetic drug interactions via cytochrome P450 enzymes and P-glycoprotein, presumably caused by hyperforin. In a phase I, open-label, non-randomized, single-sequence study, the low-hyperforin Hypericum extract Ze 117 was investigated using a drugs cocktail in 20 healthy volunteers. No pharmacokinetic interactions of Ze 117 were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4 and P-glycoprotein...
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739322/impact-of-oncology-drug-shortages-on-chemotherapy-treatment
#8
Abby Alpert, Mireille Jacobson
Prescription drug shortages began to increase markedly in the mid-2000s, including sterile injectable products such as chemotherapy drugs. Using Medicare claims linked to Surveillance Epidemiology and End Results (SEER), we examined outpatient chemotherapy use during shortage periods relative to the months before and after a shortage for newly diagnosed patients with breast, colorectal, leukemia, lung, lymphoma, ovarian or pancreatic cancer (N=182,470). For most drugs, we found little impact of shortages on either the fraction of patients receiving that drug or the quantity provided...
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739321/response-to-methodological-considerations-on-cyp2d6-phenoconversion-due-to-drug-drug-interaction
#9
Kelsey West, Andrew A Monte
No abstract text is available yet for this article.
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739316/-asian-phenotype-underestimates-the-genetic-diversity-of-asia-yet-overstates-its-impact-on-variability-in-drug-disposition-and-pharmacodynamics
#10
Rominder Singh, Yik Ying Teo
No abstract text is available yet for this article.
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739315/contemporary-drug-drug-interactions-in-hiv-treatment
#11
Aaron S Devanathan, Daijha J C Anderson, Mackenzie L Cottrell, Erin M Burgunder, Ashley C Saunders, Angela D M Kashuba
Despite development of modern antiretrovirals with lower drug interaction potential than their predecessors, drug interaction challenges remain. Standard treatment regimens still require multiple antiretrovirals that may cause, or may be the target of, drug interactions. Additionally, people living with HIV are living longer, and often present with comorbid conditions that require concomitant long-term drug therapy. Also, treatment of infectious diseases in resource-limited settings can result in significant interactions...
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739312/polymorphic-variants-in-nr1i3-and-ugt2b7-predict-taxane-neurotoxicity-and-have-prognostic-relevance-in-breast-cancer-patients-a-case-control-study
#12
Mariamena Arbitrio, Francesca Scionti, Emanuela Altomare, Maria Teresa Di Martino, Giuseppe Agapito, Teresa Galeano, Nicoletta Staropoli, Eleonora Iuliano, Francesco Grillone, Fernanda Fabiani, Daniele Caracciolo, Mario Cannataro, Grazia Arpino, Daniele Santini, Pierfrancesco Tassone, Pierosandro Tagliaferri
Taxane-related peripheral neuropathy (TrPN) is a dose-limiting toxicity with important inter-individual variability. Genetic polymorphisms in ADME genes may account for variability in drug efficacy and/or toxicity. By the use of Affymetrix DMETTM microarray platform, in a retrospective case-control study, the correlation between ADME polymorphic variants and grade ≥2-3 TrPN (G≥2-3 TrPN) was investigated. In a breast cancer (BC) training set, 5 SNPs in NR1I3 and UGT2B7genes were correlated to G≥2-3-TrPN protection...
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739311/methodological-considerations-on-cyp2d6-phenoconversion-due-to-drug-drug-interaction
#13
LETTER
Victoria C Ziesenitz, Gerd Mikus
No abstract text is available yet for this article.
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30739310/the-us-food-and-drug-administration-centers-for-regulatory-science-and-innovation-current-activities-and-future-promise-to-accelerate-innovations
#14
Frank F Weichold
No abstract text is available yet for this article.
February 10, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30723889/human-cardiac-ventricular-like-organoid-chambers-and-tissue-strips-from-pluripotent-stem-cells-as-a-two-tiered-assay-for-inotropic-responses
#15
Wendy Keung, Patrick K W Chan, Peter C Backeris, Eugene K Lee, Nicodemus Wong, Andy O T Wong, Gabriel K Y Wong, Camie W Y Chan, Bernard Fermini, Kevin D Costa, Ronald A Li
Traditional drug discovery is an inefficient process. Human pluripotent stem cell-derived cardiomyocytes can potentially fill the gap between animal and clinical studies, but conventional 2D cultures inadequately recapitulate the human cardiac phenotype. Here, we systematically examined the pharmacological responses of engineered human ventricular-like cardiac tissue strips (hvCTS) and organoid chambers (hvCOC) to 25 cardioactive compounds covering various drug classes. While hvCTS effectively detected negative and null inotropic effects, the sensitivity to positive inotropes was modest...
February 5, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30723888/model-informed-drug-development-approach-to-expedite-approval-case-of-alectinib-in-first-line-anaplastic-lymphoma-kinase-non-small-cell-lung-cancer
#16
Peter N Morcos, Jiang Liu, Gideon M Blumenthal, Hong Zhao
No abstract text is available yet for this article.
February 5, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30703255/positive-and-negative-effects-of-cannabis-and-cannabinoids-on-health
#17
REVIEW
Koby Cohen, Abraham Weizman, Aviv Weinstein
Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term side effects including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia and mood disorders. However, casual relations between cannabis use and these adverse effects are missing. On the other hand, recent research proposed promising therapeutic potential of cannabinoid-based drugs for a wide range of medical conditions including neurological and psychiatric disorders...
January 31, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30697693/comparison-of-different-strategies-to-measure-medication-adherence-via-claims-data-in-patients-with-chronic-heart-failure
#18
Peter Ihle, Katrin Krueger, Ingrid Schubert, Nina Griese-Mammen, Natalie Parrau, Ulrich Laufs, Martin Schulz
Medication adherence correlates with morbidity and mortality in patients with chronic heart failure (CHF), but is difficult to assess. We conducted a retrospective methodological cohort study in 3,808 CHF patients calculating adherence as proportion of days covered (PDC) utilizing claims data from 2010 to 2015. We aimed to compare different parameters' influence on the PDC of elderly CHF patients exemplifying a complex chronic disease. Investigated parameters were the assumed prescribed daily dose (PDD), stockpiling, and periods of hospital stay...
January 29, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30690722/hypersensitivity-and-cardiovascular-risks-related-to-allopurinol-and-febuxostat-therapy-in-asians-a-population-based-cohort-study-and-meta-analysis
#19
Chi-Hua Chen, Chun-Bing Chen, Chee Jen Chang, Yu Jr Lin, Chuang-Wei Wang, Ching-Chi Chi, Chun-Wei Lu, Wei-Ti Chen, Ren-You Pan, Shih-Chi Su, Lung-An Hsu, Ya-Ching Chang, Kuang-Hui Yu, Yeong-Jian Jan Wu, Ko-Ming Lin, Shuen-Iu Hung, Shin-Ming Chen, Wen-Hung Chung
The safety of newer xanthine oxidase inhibitor-febuxostat comparing to allopurinol remains unclear. To compare the risks of allopurinol- and febuxostat-hypersensitivity and cardiovascular diseases (CVD) in Asians, we conducted a population-based cohort study enrolling patients receiving allopurinol or febuxostat from Chang Gung Memorial Hospital Health System across Taiwan during 2012-2016 and further performed a meta-analysis incorporating two recent studies. Among the 61,539 users, a corresponding 12,007 and 5,680 patients were identified as new users...
January 28, 2019: Clinical Pharmacology and Therapeutics
https://read.qxmd.com/read/30673124/inter-individual-and-regional-variability-in-drug-transporter-abundance-at-the-human-blood-brain-barrier-measured-by-quantitative-targeted-proteomics
#20
Sarah Billington, Laurent Salphati, Cornelis E C A Hop, Xiaoyan Chu, Raymond Evers, Doug Burdette, Christopher Rowbottom, Yurong Lai, Guangqing Xiao, W Griffith Humphreys, Tot Bui Nguyen, Bhagwat Prasad, Jashvant D Unadkat
For in-vitro to in-vivo extrapolation (IVIVE) of brain distribution of drugs that are transported at the human blood-brain barrier (BBB), it's important to quantify the inter-individual and regional variability of drug transporter abundance at this barrier. Therefore, using quantitative targeted proteomics, we compared the abundance of ABC and SLC transporters in brain microvascular endothelial cells (BMEC) isolated from post-mortem specimens of two matched brain regions, the occipital (BA17) and parietal (BA39) lobe, from 30 adults...
January 23, 2019: Clinical Pharmacology and Therapeutics
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