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sex differences, pharmacokinetics

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https://www.readbyqxmd.com/read/29761517/pharmacokinetics-of-intravenous-gentamicin-in-healthy-young-adult-compared-to-aged-alpacas
#1
A Gestrich, D Bedenice, M Ceresia, I Zaghloul
The study objective was to evaluate the effects of age on aminoglycoside pharmacokinetics in eight young-adult (<4 years) and eight aged (≥14 years) healthy alpacas, receiving a single 6.6 mg/kg intravenous gentamicin injection. Heparinized plasma samples were obtained at designated time points following drug administration and frozen at -80°C until assayed by a validated immunoassay (QMS® ). Compartmental and noncompartmental analyses of gentamicin plasma concentrations versus time were performed using WinNonlin (v6...
May 14, 2018: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29755544/physicochemical-stress-degradation-evaluation-and-pharmacokinetic-study-of-azgh101-a-new-synthesized-cox2-inhibitor-after-i-v-and-oral-administration-in-male-and-female-rats
#2
Hoda Bahmanof, Simin Dadashzadeh, Afshin Zarghi, Alireza Shafaati, Seyed Mohsen Foroutan
Nonsteroidal anti-inflammatory drugs (NSAIDs) act mainly via inhibition of prostaglandins synthesis by inhibition of cyclooxygenase (COX) isoenzymes (COX-1 and COX-2). Selective COX-2 inhibitors which are also known as coxibs provide the main therapeutic effects of NSAIDs. Zarghi et al . reported 6-benzoyl-2-(4-(methylsulfonyl) phenyl) quinoline-4-carboxylic acid (AZGH101) as a novel derivative of ketoprofen with improved selectivity index (COX-1/COX-2 inhibitory potency) in comparison with ketoprofen. In this study, the log P and stability of AZGH101 were evaluated and the pharmacokinetic characteristics of this compound were investigated following intravenous (10 mg/kg), and oral administration (20 mg/kg), to Wistar rats...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29746956/liposomal-delivery-of-a-pin1-inhibitor-complexed-with-cyclodextrins-as-new-therapy-for-high-grade-serous-ovarian-cancer
#3
Concetta Russo Spena, Lucia De Stefano, Stefano Palazzolo, Barbara Salis, Carlotta Granchi, Filippo Minutolo, Tiziano Tuccinardi, Roberto Fratamico, Sara Crotti, Sara D'Aronco, Marco Agostini, Giuseppe Corona, Isabella Caligiuri, Vincenzo Canzonieri, Flavio Rizzolio
Pin1, a prolyl isomerase that sustains tumor progression, is overexpressed in different types of malignancies. Functional inactivation of Pin1 restrains tumor growth and leaves normal cells unaffected making it an ideal pharmaceutical target. Although many studies on Pin1 have focused on malignancies that are influenced by sex hormones, studies in ovarian cancer have lagged behind. Here, we show that Pin1 is an important therapeutic target in high-grade serous epithelial ovarian cancer. Knock down of Pin1 in ovarian cancer cell lines induces apoptosis and restrains tumor growth in a syngeneic mouse model...
May 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29725997/population-pharmacokinetic-pharmacodynamic-analysis-of-alirocumab-in-healthy-volunteers-or-hypercholesterolemic-subjects-using-an-indirect-response-model-to-predict-low-density-lipoprotein-cholesterol-lowering-support-for-a-biologics-license-application-submission
#4
Xavier Nicolas, Nassim Djebli, Clémence Rauch, Aurélie Brunet, Fabrice Hurbin, Jean-Marie Martinez, David Fabre
BACKGROUND: Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels. OBJECTIVE: This analysis aimed to develop and qualify a population pharmacokinetic/pharmacodynamic model for alirocumab based on pooled data obtained from 13 phase I/II/III clinical trials. METHODS: From a dataset of 2799 individuals (14,346 low-density lipoprotein-cholesterol values), individual pharmacokinetic parameters from the population pharmacokinetic model presented in Part I of this series were used to estimate alirocumab concentrations...
May 3, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29702137/reduced-clearance-of-venlafaxine-in-a-combined-treatment-with-quetiapine
#5
Michael Paulzen, Georgios Schoretsanitis, Christoph Hiemke, Gerhard Gründer, Ekkehard Haen, Marc Augustin
Venlafaxine and the atypical antipsychotic quetiapine are often administered concomitantly. Both drugs share several metabolic hepatic pathways. However, pharmacokinetic interactions between venlafaxine and quetiapine have not been studied yet. A therapeutic drug monitoring database containing serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. Two groups of patients were compared: venlafaxine monotherapy V0 (n = 153) and co-medication with quetiapine, VQUE (n = 71)...
April 24, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29696400/put-gender-glasses-on-the-effects-of-phenolic-compounds-on-cardiovascular-function-and-diseases
#6
REVIEW
Ilaria Campesi, Maria Marino, Manuela Cipolletti, Annalisa Romani, Flavia Franconi
INTRODUCTION: The influence of sex and gender is particularly relevant in cardiovascular diseases (CVD) as well as in several aspects of drug pharmacodynamics and pharmacokinetics. Anatomical and physiological differences between the sexes may influence the activity of many drugs, including the possibility of their interaction with other drugs, bioactive compounds, foods and beverages. Phenolic compounds could interact with our organism at organ, cellular, and molecular levels triggering a preventive action against chronic diseases, including CVD...
April 25, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29689539/maximizing-the-benefits-of-hiv-preexposure-prophylaxis
#7
Susan P Buchbinder
Preexposure prophylaxis (PrEP) with tenofovir/emtricitabine (slash indicates coformulation) is highly effective in preventing new HIV infections. PrEP efficacy is strongly associated with adherence. In clinical trials, PrEP has been more effective in men who have sex with men and HIV-serodiscordant heterosexual couples than in women, likely reflecting pharmacokinetic differences between levels of tenofovir disoproxil fumarate in vaginal and rectal tissues, and poorer adherence in studies in women. Current guidelines recommend daily PrEP for men and women; however, PrEP taken at least 4 days per week for men may be as effective as daily PrEP, and women must take PrEP 6 to 7 days per week to maximize efficacy...
April 2018: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/29679474/population-pharmacokinetics-of-gliclazide-in-normal-and-diabetic-rabbits
#8
Mastan Shaik, Shabana Shaik, Eswar Kumar Kilari
Gliclazide is a second-generation sulphonylurea drug widely used in the treatment of type 2 diabetes. However, there is no single report to describe the population pharmacokinetics of gliclazide in animal models. This study was aimed to evaluate the population pharmacokinetics (PK) of gliclazide in normal and alloxan-induced diabetic rabbits using nonlinear mixed effects modeling. A total of 90 New Zealand white rabbits were administered with 3 doses (4.13, 8.27 and 16.53 mg/kg b.wt) of gliclazide by an oral route...
April 21, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29671013/ontogeny-of-cocaine-induced-behaviors-and-cocaine-pharmacokinetics-in-male-and-female-neonatal-preweanling-and-adult-rats
#9
Sanders A McDougall, Matthew G Apodaca, Alena Mohd-Yusof, Adrian D Mendez, Caitlin G Katz, Angie Teran, Israel Garcia-Carachure, Anthony T Quiroz, Cynthia A Crawford
RATIONALE: Ontogenetic differences in the behavioral responsiveness to cocaine have often been attributed to the maturation of dopaminergic elements (e.g., dopamine transporters, D2High receptors, receptor coupling, etc.). OBJECTIVE: The purpose of this study was to determine whether ontogenetic changes in cocaine pharmacokinetics might contribute to age-dependent differences in behavioral responsiveness. METHODS: Male and female neonatal (PD 5), preweanling (PD 10 and PD 20), and adult (PD 70) rats were injected (IP) with cocaine or saline and various behaviors (e...
April 18, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29650353/reprint-of-environmental-toxicology-and-omics-a-question-of-sex
#10
Xuefang Liang, April Feswick, Denina Simmons, Christopher J Martyniuk
Molecular initiating events and downstream transcriptional/proteomic responses provide valuable information for adverse outcome pathways, which can be used predict the effects of chemicals on physiological systems. There has been a paucity of research that addresses sex-specific expression profiling in toxicology and due to cost, time, and logistic considerations, sex as a variable has not been widely considered. In response to this deficiency, federal agencies in the United States, Canada, and Europe have highlighted the importance of including sex as a variable in scientific investigations...
April 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29556934/a-limited-sampling-strategy-to-estimate-exposure-of-everolimus-in-whole-blood-and-peripheral-blood-mononuclear-cells-in-renal-transplant-recipients-using-population-pharmacokinetic-modeling-and-bayesian-estimators
#11
Ida Robertsen, Jean Debord, Anders Åsberg, Pierre Marquet, Jean-Baptiste Woillard
BACKGROUND AND OBJECTIVE: Intracellular exposure of everolimus may be a better marker of therapeutic effect than trough whole blood concentrations. We aimed to develop pharmacokinetic population models and Bayesian estimators based on a limited sampling strategy for estimation of dose interval exposures of everolimus in whole blood and peripheral blood mononuclear cells (PBMCs) in renal transplant recipients. METHODS: Full whole blood and PBMC concentration-time profiles of everolimus were obtained from 12 stable renal transplant recipients on two different occasions, 4 weeks apart...
March 20, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29544105/pharmacokinetic-differences-of-mifepristone-between-sexes-in-animals
#12
Wenge Chen, Yunlong Cheng, Jianzhong Chen, Jiahang Chen, Kai Jiang, Yuyang Zhou, Lee Jia
Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes...
May 30, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29514871/interindividual-differences-in-caffeine-metabolism-and-factors-driving-caffeine-consumption
#13
REVIEW
Astrid Nehlig
Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29505133/differences-in-the-synthesis-and-elimination-of-phosphatidylethanol-16-0-18-1-and-16-0-18-2-after-acute-doses-of-alcohol
#14
Nathalie Hill-Kapturczak, Donald M Dougherty, John D Roache, Tara E Karns-Wright, Martin A Javors
BACKGROUND: The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers. METHODS: A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption...
May 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29501590/modeling-of-pharmacokinetics-efficacy-and-hemodynamic-effects-of-macitentan-in-patients-with-pulmonary-arterial-hypertension
#15
Andreas Krause, Jochen Zisowsky, Jasper Dingemanse
BACKGROUND: Macitentan is the first endothelin receptor antagonist with demonstrated efficacy on morbidity and mortality in pulmonary arterial hypertension (PAH) in the pivotal study SERAPHIN. METHODS: The pharmacokinetics (PK) of macitentan and its active metabolite, ACT-132577, were characterized in a population model. Efficacy and hemodynamics (pharmacodynamics, PD) were related to PK based on PK/PD modeling. RESULTS: Sex, age, and body weight influenced the PK to a statistically significant extent...
April 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29491835/sex-differences-in-the-effects-of-a-kappa-opioid-receptor-antagonist-in-the-forced-swim-test
#16
Abigail Laman-Maharg, Alexia V Williams, Mikaela D Zufelt, Vanessa A Minie, Stephanie Ramos-Maciel, Rebecca Hao, Evelyn Ordoñes Sanchez, Tiffany Copeland, Jill L Silverman, Angelina Leigh, Rodney Snyder, F Ivy Carroll, Timothy R Fennell, Brian C Trainor
There is growing evidence that kappa opioid receptor (KOR) antagonists could be a useful class of therapeutics for treating depression and anxiety. However, the overwhelming majority of preclinical investigations examining the behavioral effects of KOR antagonists have been in male rodents. Here, we examined the effects of the long-acting KOR antagonist nor-binaltophimine (norBNI) on immobility in the forced swim test in males and females of two different rodent species (C57Bl/6J and California mice). Consistent with previous reports, norBNI (10 mg/kg) decreased immobility in the forced swim test for male C57Bl/6J and California mice...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29484612/sex-differences-in-reported-adverse-drug-reactions-of-selective-serotonin-reuptake-inhibitors
#17
Corine Ekhart, Florence van Hunsel, Joep Scholl, Sieta de Vries, Eugene van Puijenbroek
INTRODUCTION: Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men. OBJECTIVE: The aim of this explorative study was to investigate whether differences exist in reported ADRs of selective serotonin reuptake inhibitors (SSRIs) for men and women in the database of the Netherlands Pharmacovigilance Centre Lareb. METHODS: A ratio of reports concerning women and men, corrected for the number of users, was calculated for all the ADRs reported on SSRIs...
February 26, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29468507/impact-of-clinical-factors-and-ugt1a9-and-cyp2b6-genotype-on-inter-individual-differences-in-propofol-pharmacokinetics
#18
Akihiro Kanaya, Toshihiro Sato, Nobuo Fuse, Hiroaki Yamaguchi, Nariyasu Mano, Masanori Yamauchi
PURPOSE: Propofol is one of the most widely used fast-acting intravenously administered anesthetics. However, although large inter-individual differences in dose requirements and recovery time have been observed, there are few previous studies in which the association between several potential covariates, including genetic factors such as the UGT1A9 and CYP2B6 genotypes, and propofol pharmacokinetics was simultaneously examined. This study aimed to identify factors determining propofol pharmacokinetics...
April 2018: Journal of Anesthesia
https://www.readbyqxmd.com/read/29462364/bioavailability-and-pharmacokinetics-of-oral-cocaine-in-humans
#19
Marion A Coe, Rebecca A Jufer Phipps, Edward J Cone, Sharon L Walsh
The pharmacokinetic profile of oral cocaine has not been fully characterized and prospective data on oral bioavailability are limited. A within-subject study was performed to characterize the bioavailability and pharmacokinetics of oral cocaine. Fourteen healthy inpatient participants (six males) with current histories of cocaine use were administered two oral doses (100 and 200 mg) and one intravenous (IV) dose (40 mg) of cocaine during three separate dosing sessions. Plasma samples were collected for up to 24 h after dosing and analyzed for cocaine and metabolites by gas chromatography-mass spectrometry...
February 15, 2018: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29457876/pharmacokinetics-of-metformin-in-patients-with-gastrointestinal-intolerance
#20
Laura J McCreight, Tore B Stage, Paul Connelly, Mike Lonergan, Flemming Nielsen, Cornelia Prehn, Jerzy Adamski, Kim Brøsen, Ewan R Pearson
AIMS: To assess potential causes of metformin intolerance, including altered metformin uptake from the intestine, increased anaerobic glucose utilization and subsequent lactate production, altered serotonin uptake, and altered bile acid pool. METHODS: For this pharmacokinetic study, we recruited 10 severely intolerant and 10 tolerant individuals, matched for age, sex and body mass index. A single 500-mg dose of metformin was administered, with blood sampling at 12 time points over 24 hours...
February 19, 2018: Diabetes, Obesity & Metabolism
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