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Clinical Pharmacology and Therapeutics

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https://www.readbyqxmd.com/read/28317101/recent-advances-in-small-molecule-and-biological-therapeutic-approaches-in-the-treatment-of-psoriasis
#1
Jackson G Turbeville, Nupur U Patel, Leah A Cardwell, Elias Oussedik, Steven R Feldman
New treatments continue to be developed for psoriasis. In this review, we aim to summarize the results of the major published studies on biologic and small molecule drugs for the treatment of psoriasis. We emphasize the safety, efficacy, and tolerability of these treatment options. A review of the MEDLINE database was conducted for each class of medication. Randomized controlled trials were identified for each medication; data on efficacy, safety, and tolerability was reviewed. Biologic and small molecule treatment options are more effective than placebo, although there were few head-to-head trials to assess relative efficacy between biologics and small molecule treatments...
March 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28295269/role-and-value-of-clinical-pharmacy-in-heart-failure-management
#2
Wendy Gattis Stough, J Herbert Patterson
Effectively managing heart failure requires a multi-disciplinary, holistic approach attuned to many factors: diagnosis of structural and functional cardiac abnormalities; medication, device, or surgical management; concomitant treatment of comorbidities; physical rehabilitation; dietary considerations; and social factors. This practice paper highlights the pharmacist's role in the management of patients with heart failure, the evidence supporting their functions, and steps to ensure the pharmacist resource is available to the broad population of patients with heart failure...
March 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28295243/quantitative-contribution-of-rs75017182-to-dihydropyrimidine-dehydrogenase-mrna-splicing-and-enzyme-activity
#3
Qian Nie, Shikshya Shrestha, Erin E Tapper, Colbren S Trogstad-Isaacson, Kelly J Bouchonville, Adam M Lee, Rentian Wu, Calvin R Jerde, Zhiquan Wang, Phillip A Kubica, Steven M Offer, Robert B Diasio
Dihydropyrimidine dehydrogenase (DPD; DPYD gene) variants have emerged as reliable predictors of adverse toxicity to the chemotherapy agent 5-fluorouracil (5-FU). The intronic DPYD variant rs75017182 has been recently suggested to promote alternative splicing of DPYD. However, both the extent of alternative splicing and the true contribution of rs75017182 to DPD function remain unclear. In the present study we quantified alternative splicing and DPD enzyme activity in rs75017182 carriers utilizing healthy volunteer specimens from the Mayo Clinic Biobank...
March 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28295240/pharmacogenomic-advances-in-the-prediction-and-prevention-of-cutaneous-idiosyncratic-drug-reactions
#4
Ren-You Pan, Ro-Lan Dao, Shuen-Iu Hung, Wen-Hung Chung
Cutaneous idiosyncratic drug reactions (CIDRs) are usually unpredictable, ranging from mild maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs) such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing evidences suggest HLA alleles are strongly associated with drug-induced-CIDRs. The pathomechanisms for CIDRs include genetic polymorphisms affecting complex immune specific HLA/drug antigen/T cell receptor interactions and drug metabolism...
March 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28295239/eculizumab-dosing-regimen-in-atypical-hus-possibilities-for-individualized-treatment
#5
Elena Volokhina, Kioa Wijnsma, Renate van der Molen, Nel Roeleveld, Thea van der Velden, Joop Goertz, Fred Sweep, Roger J Brüggemann, Jack Wetzels, Nicole van de Kar, Lambertus van den Heuvel
Recent studies indicate that eculizumab is often given in excess to aHUS patients. Individualization of treatment is thus highly requested, however, data on pharmacokinetics and pharmacodynamics of eculizumab remain limited. We analyzed 11 patients during induction (weekly), maintenance (2-weekly) and tapering (every 3-8 weeks) phases of treatment. The trough eculizumab levels increased with each additional dose during the induction phase (depending on body weight). During maintenance, high eculizumab concentrations of up to 772 µg/mL were observed...
March 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28295236/pharmacology-and-therapeutics-education-in-eu-needs-harmonisation-and-modernisation-a-cross-sectional-survey-among-185-medical-schools-in-27-countries
#6
D J Brinkman, J Tichelaar, M Okorie, L Bissell, T Christiaens, R Likic, R Mačiulaitis, J Costa, E J Sanz, B I Tamba, S R Maxwell, M C Richir, M A van Agtmael
Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students' preparedness for prescribing. 185 medical schools (64%) from 27 EU countries responded...
March 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28295234/adverse-drug-reactions-in-children-the-double-edged-sword-of-therapeutics
#7
Abdelbaset A Elzagallaai, Michael J E Greff, Michael J Rieder
Adverse drug reactions (ADRs) represent a major health problem worldwide with high morbidity and mortality rates. ADRs are classified into type A (augmented) and type B (bizarre) ADRs with the former group being more common and the later less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of Off-label and unlicensed use of drugs...
March 13, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28224612/clopidogrel-paclitaxel-drug-drug-interaction-a-pharmacoepidemiologic-study
#8
K Agergaard, M Mau-Sørensen, T B Stage, T L Jørgensen, R E Hassel, K D Steffensen, J W Pedersen, M L H Milo, S H Poulsen, A Pottegård, J Hallas, K Brøsen, T K Bergmann
Paclitaxel is mainly eliminated by CYP2C8 in the liver. CYP2C8 is strongly inhibited by the clopidogrel metabolite acyl-β-D-glucuronide. To determine if this interaction has clinical relevance, we identified 48 patients treated with clopidogrel and paclitaxel using databases and a prescription register. Peripheral sensory neuropathy was retrospectively evaluated from medical charts and compared to that of 88 age and sex matched controls treated with paclitaxel and low dose aspirin. By a cumulative dose of 1500 mg paclitaxel, 35% of the patients had developed severe neuropathy...
February 22, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28224611/response-to-ppar%C3%AE-modulation-by-gw501516-an-unsuccessful-exercise-mimetic
#9
LETTER
Shunchang Li, Ismail Laher
No abstract text is available yet for this article.
February 22, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28214288/an-accelerator-mass-spectrometry-enabled-microtracer-study-to-evaluate-the-first-pass-effect-on-the-absorption-of-yh4808
#10
Anhye Kim, Byung-Yong Yu, Stephen R Dueker, Kwang-Hee Shin, Hwa Suk Kim, Hyungmi Ahn, Joo-Youn Cho, Kyung-Sang Yu, In-Jin Jang, Howard Lee
(14) C-labeled YH4808, a novel potassium-competitive acid blocker, was intravenously administered as a microtracer at 80 μg (11.8 kBq or 320 nCi) concomitantly with the non-radiolabeled oral drug at 200 mg to determine the absolute bioavailability and to assess the effect of pharmacogenomics on the oral absorption of YH4808. The absolute bioavailability was low and highly variable (mean, 10.1%; range, 2.3-19.3%), and M3 and M8, active metabolites of YH4808, were formed 22.6- and 38.5-fold higher after oral administration than intravenous administration, respectively...
February 18, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28198005/clinical-pharmacogenetics-implementation-consortium-cpic-guideline-for-pharmacogenetics-guided-warfarin-dosing-2017-update
#11
Julie A Johnson, Kelly E Caudle, Li Gong, Michelle Whirl-Carrillo, C Michael Stein, Stuart A Scott, Ming Ta Michael Lee, Brian F Gage, Stephen E Kimmel, Minoli A Perera, Jeffrey L Anderson, Munir Pirmohamed, Teri E Klein, Nita A Limdi, Larisa H Cavallari, Mia Wadelius
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry...
February 15, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187521/the-role-of-fcrn-in-the-pharmacokinetics-of-biologics-in-patients-with-multiple-myeloma
#12
LETTER
Joannes F M Jacobs, Diane R Mould
No abstract text is available yet for this article.
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187516/collaborating-to-compete-blood-profiling-atlas-in-cancer-bloodpac-consortium
#13
R L Grossman, B Abel, S Angiuoli, J C Barrett, D Bassett, K Bramlett, G M Blumenthal, A Carlsson, R Cortese, J DiGiovanna, B Davis-Dusenbery, R Dittamore, D A Eberhard, P Febbo, M Fitzsimons, Z Flamig, J Godsey, J Goswami, A Gruen, F O Guzman, J Han, D Hayes, J Hicks, D Holloway, D Hovelson, J Johnson, H Juhl, R Kalamegham, R Kamal, Q Kang, G J Kelloff, M Klozenbuecher, A Kolatkar, P Kuhn, K Langone, R Leary, P Loverso, H Manmathan, A-M Martin, J Martini, D Miller, M Mitchell, T Morgan, R Mulpuri, T Nguyen, G Otto, A Pathak, E Peters, R Philip, E Posadas, D Reese, M G Reese, D Robinson, A D Rossi, H Sakul, J Schageman, S Singh, H I Scher, K Schmitt, A Silvestro, J Simmons, T Simmons, J Sislow, A Talasaz, P Tang, M Tewari, S Tomlins, H Toukhy, H R Tseng, M Tuck, A Tzou, J Vinson, Y Wang, W Wells, A Welsh, J Wilbanks, J Wolf, L Young, J S H Lee, L C Leiman
The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort amongst academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g. clinical diagnosis, treatment history and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187513/collaboration-to-accelerate-proteogenomics-cancer-care-the-department-of-veterans-affairs-department-of-defense-and-the-national-cancer-institute-s-applied-proteogenomics-organizational-and-learning-apollo-network
#14
L D Fiore, H Rodriguez, C D Shriver
The ability to interrogate cancer at the proteogenomic level has the potential to transform oncology care from trial-and-error treatment strategies based on the anatomy and genomic profiling of tumors to one that is precisely based on the tumor's molecular profile. The next step in the evolution of precision oncology is developing proteogenomic approaches that make no exclusive assumptions a priori as to the molecular level of the patient's disease. The DoD, VA, and NCI responded to the Cancer Moonshot initiative by linking each agency's unique capabilities in clinical and basic science, computing, and high-throughput sequencing...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187506/the-effect-of-gene-variants-on-levonorgestrel-pharmacokinetics-when-combined-with-antiretroviral-therapy-containing-efavirenz-or-nevirapine
#15
M Neary, M Lamorde, A Olagunju, K M Darin, C Merry, P Byakika-Kibwika, D J Back, M Siccardi, A Owen, K K Scarsi
Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2 and NR1I3 were analysed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based ART, in comparison to ART-naïve women using multivariate linear regression...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187497/antiretroviral-therapy-with-efavirenz-accentuates-pregnancy-associated-reduction-of-dihydroartemisinin-piperaquine-exposure-during-malaria-chemoprevention
#16
Richard Kajubi, Liusheng Huang, Prasanna Jagannathan, Nona Chamankhah, Moses Were, Theodore Ruel, Catherine A Koss, Abel Kakuru, Norah Mwebaza, Moses Kamya, Diane Havlir, Grant Dorsey, Philip J Rosenthal, Francesca T Aweeka
Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant women receiving efavirenz, and in 30 HIV-uninfected non-pregnant women. DHA peak concentration and area under the concentration time curve (AUC0-8hr ) were 50% and 47% lower, respectively, and piperaquine AUC0-21d was 40% lower in pregnant women compared to non-pregnant women...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187492/are-evidence-standards-different-for-genomic-vs-clinical-based-precision-medicine-a-quantitative-analysis-of-individualized-warfarin-therapy
#17
Devender S Dhanda, Gregory F Guzauskas, Josh J Carlson, Anirban Basu, David L Veenstra
Evidence requirements for implementation of precision medicine (PM), whether informed by genomic or clinical data, are not well defined. Evidence requirements are driven by uncertainty and its attendant consequences; these aspects can be quantified by a novel technique in health economics, value of information analysis (VOI). We utilized VOI analysis to compare the evidence levels over time for warfarin dosing based on pharmacogenomic- vs. amiodarone-warfarin drug-drug interaction information. The primary outcome was the expected value of perfect information (EVPI), which is an estimate of the upper limit of the societal value of conducting future research...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28182291/pharmacogenetics-of-voriconazole-cyp2c19-but-also-cyp3a4-need-to-be-genotyped
#18
LETTER
Elodie Gautier-Veyret, Xavier Fonrose, Françoise Stanke-Labesque
No abstract text is available yet for this article.
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28182281/essential-medicines-for-children
#19
Hoppu Kalle
WHO defines Essential medicines as those that satisfy the priority health-care needs of the population (1). The right to Essential medicines has been considered an important component of the right to health. In the name of equity children should also have access to appropriate, available, affordable, and quality essential medicines they need, but children's essential medicines are too often missing. This article is protected by copyright. All rights reserved.
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28182275/charting-a-course-for-precision-oncology
#20
Dimitri Kusnezov, Jason Paragas
Fields of science have undergone dramatic reorganizations as they have come to terms with the realities of the growing complexities of their problem set, the costs, and the breadth of skills needed to make major progress. Precision medicine, Cancer Moonshot, and changes in computing technology are providing an opportunity for this field to redefine its course. This article is protected by copyright. All rights reserved.
February 9, 2017: Clinical Pharmacology and Therapeutics
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