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Pharmacokinetics pharmacodynamics

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https://www.readbyqxmd.com/read/29150952/ck-2127107-amplifies-skeletal-muscle-response-to-nerve-activation-in-humans
#1
Jinsy A Andrews, Timothy M Miller, Vipin Vijayakumar, Randall Stoltz, Joyce K James, Lisa Meng, Andrew A Wolff, Fady I Malik
INTRODUCTION: Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy subjects. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans. METHODS: To assess the force-frequency response, subjects received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study...
November 18, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/29150291/ruxolitinib-conjugated-gold-nanoparticles-for-topical-administration-an-alternative-for-treating-alopecia
#2
Sanda Boca, Cristian Berce, Ancuta Jurj, Bobe Petrushev, Laura Pop, Grigore-Aristide Gafencu, Sonia Selicean, Vlad Moisoiu, Daiana Temian, Wilhelm-Thomas Micu, Simion Astilean, Cornelia Braicu, Ciprian Tomuleasa, Ioana Berindan-Neagoe
Alopecia is a dermatological condition for which Janus kinase (JAK) inhibitors have recently emerged as potential therapy options, but with limited practical use because of the systemic side effects. The topical use of Ruxolitinib in alopecia universalis has been demonstrated, but little is known about the pharmacodynamics and pharmacokinetics of this way of administration. Nanomedicine provides improved therapeutics. In the current paper we present preliminary data regarding the potential use of Ruxolitinib-conjugated gold nanoparticles (GNPs) in dermatological conditions, as GNPs have been proven to have a reduced absorption rate into the systemic blood flow for cutaneous administration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150269/potential-role-of-the-virchow-robin-space-in-the-pathogenesis-of-bacterial-meningitis
#3
Patrick Chan, Denis J Meerdink, James A Uchizono
Meningitis is an infectious disease commonly arising from a bacterial etiology. The rapid progression of morbidity and mortality due to bacterial meningitis requires critical and imminent time-dependent clinical intervention. Although it is unambiguously clear that bacteria must infiltrate the cerebrospinal fluid, the sequence of events in the pathogenesis of bacterial meningitis has not been fully elucidated. Most reviews of the pathogenesis of bacterial meningitis do not specify the anatomical location of bacteria following BBB traversal...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149294/pharmacokinetics-pharmacodynamics-of-systemically-administered-polymyxin-b-against-klebsiella-pneumoniae-in-mouse-thigh-and-lung-infection-models
#4
Cornelia B Landersdorfer, Jiping Wang, Veronika Wirth, Ke Chen, Keith S Kaye, Brian T Tsuji, Jian Li, Roger L Nation
Background: The pharmacokinetic/pharmacodynamic (PK/PD) relationship for polymyxin B against Klebsiella pneumoniae infections is not known. Methods: Dose-fractionation studies with subcutaneous polymyxin B were conducted in neutropenic mice in which infection with three strains of K. pneumoniae had been produced in thighs or lungs. Dosing (thigh infection 0.5-120 mg/kg/day; lung infection 5-120 mg/kg/day) commenced 2 h after inoculation, and bacterial burden was measured 24 h later...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29149154/philosophical-issues-and-psychological-variables-that-influence-the-determination-of-opioid-effectiveness-a-narrative-review
#5
Daniel Michael Doleys
BACKGROUND: The prescribing of opioids in the chronic pain setting is often based on the pharmacodynamics, pharmacokinetics, and pharmacogenetics of the drug obtained during development and clinical trials. However, the effectiveness of opioids varies widely and often appears to bear no relationship to the aforementioned variables. The impact of philosophical issues and psychological factors on determining how clinically effective opioid therapy is has often been over looked. OBJECTIVES: This manuscript provides a selective review and narrative summary of the philosophical issues and psychological factors which can influence opioid effectiveness...
November 2017: Pain Physician
https://www.readbyqxmd.com/read/29145933/quantitative-structure-pharmacokinetics-relationships-for-plasma-protein-binding-of-basic-drugs
#6
Zvetanka Dobreva Zhivkova
PURPOSE: Binding of drugs to plasma proteins is a common physiological occurrence which may have a profound effect on both pharmacokinetics and pharmacodynamics. The early prediction of plasma protein binding (PPB) of new drug candidates is an important step in drug development process. The present study is focused on the development of quantitative structure - pharmacokinetics relationship (QSPkR) for the negative logarithm of the free fraction of the drug in plasma (pfu) of basic drugs...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29143669/considerations-for-using-minocycline-vs-doxycycline-for-treatment-of-canine-heartworm-disease
#7
Mark G Papich
BACKGROUND: Doxycycline has been considered the first drug of choice for treating Wolbachia, a member of the Rickettsiaceae, which has a symbiotic relationship with filarial worms, including heartworms. Wolbachia, is susceptible to tetracyclines, which have been used as adjunctive treatments for heartworm disease. Treatment with doxycycline reduces Wolbachia numbers in all stages of heartworms and improves outcomes and decreased microfilaremia in dogs treated for heartworm disease. The American Heartworm Society recommends treatment with doxycycline in dogs diagnosed with heartworm disease at a dose of 10 mg/kg twice daily for 28 days...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29143550/safety-and-tolerability-of-inebilizumab-medi-551-an-anti-cd19-monoclonal-antibody-in-patients-with-relapsing-forms-of-multiple-sclerosis-results-from-a-phase-1-randomised-placebo-controlled-escalating-intravenous-and-subcutaneous-dose-study
#8
Mark A Agius, Gabriela Klodowska-Duda, Maciej Maciejowski, Andrzej Potemkowski, Jing Li, Kaushik Patra, Jacob Wesley, Soraya Madani, Gerard Barron, Eliezer Katz, Armando Flor
BACKGROUND: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19(+) B cells. OBJECTIVES: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS. METHODS: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19(+) B-cell count to ⩾80 cells/µL...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29142982/a-single-and-multiple-dose-multicenter-study-of-etelcalcetide-in-japanese-hemodialysis-patients-with-secondary-hyperparathyroidism
#9
Keitaro Yokoyama, Masafumi Fukagawa, Takashi Shigematsu, Takashi Akiba, Akifumi Fujii, Akinori Yamauchi, Motoi Odani, Tadao Akizawa
Introduction: The pharmacokinetics, pharmacodynamics, and safety and tolerability profile of etelcalcetide (ONO-5163/AMG 416), a novel, i.v., long-acting calcium-sensing receptor agonist, were studied in Japanese hemodialysis patients with secondary hyperparathyroidism. Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisted of a single dose part and a multiple dose (3 times weekly for 4 weeks) part. Major inclusion criteria were hemodialysis for at least 90 days, serum intact parathyroid hormone (iPTH) ≥ 300 pg/ml, and serum albumin-corrected Ca (cCa) ≥ 9...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29142459/a-phase-i-study-of-different-doses-and-frequencies-of-pegylated-recombinant-human-granulocyte-colony-stimulating-factor-peg-rhg-csf-in-patients-with-standard-dose-chemotherapy-induced-neutropenia
#10
Yan Qin, Xiaohong Han, Lin Wang, Ping Du, Jiarui Yao, Di Wu, Yuanyuan Song, Shuxiang Zhang, Le Tang, Yuankai Shi
Objective: The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Methods: Eligible patients received 3-cycle chemotherapy every 3 weeks...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29141139/the-effect-of-synthetic-high-density-lipoproteins-modification-with-polyethylene-glycol-on-pharmacokinetics-and-pharmacodynamics
#11
Dan Li, Maria V Fawaz, Emily E Morin, Ran Ming, Denis Sviridov, Jie Tang, Rose Ackerman, Karl Olsen, Alan T Remaley, Anna Schwendeman
Synthetic high density lipoprotein nanoparticles (sHDL) capable of mobilizing excess cholesterol from atherosclerotic arteries and delivering it to the liver for elimination have been shown to reduce plaque burden in patients. Unfortunately, sHDLs have a narrow therapeutic index and relative to the endogenous HDL shorter circulation half-life. Surface modification with polyethylene glycol (PEG) was investigated for its potential to extend sHDL circulation in vivo. Various amounts (2.5, 5 and 10%) and different chain lengths (2 and 5 kDa) of PEG-modified lipids were incorporated in sHDL's lipid membrane...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29139145/pharmacokinetic-assessment-of-the-monepantel-plus-oxfendazole-combined-administration-in-dairy-cows
#12
M Ballent, P Viviani, F Imperiale, P Dominguez, S Halwachs, H Mahnke, W Honscha, C Lanusse, G Virkel, A Lifschitz
Monepantel (MNP) is a novel anthelmintic compound launched into the veterinary pharmaceutical market. MNP is not licenced for use in dairy animals due to the prolonged elimination of its metabolite monepantel sulphone (MNPSO2 ) into milk. The goal of this study was to evaluate the presence of potential in vivo drug-drug interactions affecting the pattern of milk excretion after the coadministration of the anthelmintics MNP and oxfendazole (OFZ) to lactating dairy cows. The concentrations of both parent drugs and their metabolites were measured in plasma and milk samples by HPLC...
November 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29138563/squarticles-as-the-nanoantidotes-to-sequester-the-overdosed-antidepressant-for-detoxification
#13
Chun-Han Chen, Tse-Hung Huang, Ahmed O Elzoghby, Pei-Wen Wang, Chia-Wen Chang, Jia-You Fang
The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29138535/comparable-pharmacokinetics-and-pharmacodynamics-of-two-epoetin-alfa-formulations-eporon-%C3%A2-and-eprex-%C3%A2-following-a-single-subcutaneous-administration-in-healthy-male-volunteers
#14
Sumin Yoon, Su-Jin Rhee, Sun Ju Heo, Tae Young Oh, Seo Hyun Yoon, Joo-Youn Cho, SeungHwan Lee, Kyung-Sang Yu
Purpose: This study aimed to assess and compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties following a single subcutaneous injection of epoetin alfa (Eporon(®)) with those of the comparator (Eprex(®)) in healthy male subjects. Subjects and methods: A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29137489/androgen-deprivation-therapy-for-the-treatment-of-prostate-cancer-a-focus-on-pharmacokinetics
#15
Charles F Polotti, Christopher J Kim, Nadiya Chuchvara, Alyssa B Polotti, Eric A Singer, Sammy Elsamra
Medical therapy has undergone many changes as our understanding of prostate cancer cell biology has improved. Androgen deprivation therapy (ADT) remains the mainstay of therapy for metastatic disease. Metastatic castrate-resistant prostate cancer (CRPC) is an important concern since we are unable to stop progression with currently available agents. Areas covered: Pharmacologic ADT is the most commonly used treatment for metastatic prostate cancer. Multiple agents are available for both first-line and second-line use: antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, and CYP17 inhibitors...
November 15, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29136767/the-exposure-effect-toxicity-correlation-of-docetaxel-and-magnesium-isoglycyrrhizinate-in-non-small-cell-lung-tumor-bearing-mice
#16
Peijin Li, Suning Li, Hongmei Gu, Qianfeng Lu, Wenjiao Jiang, Xue Pei, Yilin Sun, Hongjiang Xu, Guangji Wang, Kun Hao
To take full advantage of combination therapy of Docetaxel (DTX) and Magnesium isoglycyrrhizinate (MGIG), the pharmacokinetic- pharmacodynamic- toxicodynamics (PK-PD-TD) interaction of DTX and MGIG in non-small cell lung tumor-bearing mice was investigated in the present study. A model, an integrated semi-mechanistic PK-PD-TD, was established for elucidating the exposure-effect-toxicity relationship between DTX and MGIG. A tumor growth and a transit compartmental system were applied to imitate the growth and death of tumor cell...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136540/the-application-of-in-vitro-surveillance-data-for-antibacterial-dose-selection
#17
REVIEW
Robert K Flamm, Helio S Sader, Mariana Castanheira, Ronald N Jones
In vitro surveillance data, which provide key information to interpret the results of pharmacokinetic/pharmacodynamics (PK-PD) target attainment studies, are used to support dose selection decisions and recommendations for in vitro susceptibility testing criteria for antibacterial agents during drug development. Considerations for designing the in vitro surveillance database to support the development of antibacterial agents include the choice of pathogens to study, the sample size of isolate collections needed, and target patient populations from which clinical isolates should be collected...
November 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29136343/pharmacokinetics-pharmacodynamics-and-safety-of-a-long-acting-human-growth-hormone-mod-4023-in-healthy-japanese-and-caucasian-adults
#18
William G Kramer, Michal Jaron-Mendelson, Ronit Koren, Oren Hershkovitz, Gili Hart
Daily injections of growth hormone (GH) as replacement therapy in GH-deficient (GHD) patients may cause poor compliance and inconvenience. C-terminal peptide-modified human GH (MOD-4023) has been developed for once-weekly administration in GHD adults and children. In the present study, the pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous dose of MOD-4023 were evaluated in healthy Caucasian and Japanese adults, using a phase 1 double-blind, vehicle-controlled, randomized study design...
November 14, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#19
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29135651/comparison-of-the-pharmacokinetics-and-pharmacodynamics-of-single-dose-tenofovir-vaginal-film-and-gel-formulation-fame-05
#20
Jennifer A Robinson, Mark A Marzinke, Edward J Fuchs, Rahul P Bakshi, Hans M L Spiegel, Jenell S Coleman, Lisa C Rohan, Craig W Hendrix
OBJECTIVE: While pre-exposure prophylaxis with oral tenofovir (TFV) disoproxil fumarate/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of daily vaginal gels has led to development of vaginal film formulations to improve adherence and, potentially, enable episodic use. STUDY DESIGN: In this two-arm, cross-over study of a fast-dissolving tenofovir film (40 mg) compared to a previously studied semisolid tenofovir 1% gel (40 mg), 10 healthy women received a single vaginal dose of each study product...
November 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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