Read by QxMD icon Read

sex differences, pharmacokinetics

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...
March 8, 2018: Journal of Pharmaceutical and Biomedical Analysis
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
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 in15 min. Blood and breath samples were collected before, at various times up to 360 min post-consumption, and 2, 4, 7, 11 and 14 days after alcohol consumption...
March 5, 2018: Alcoholism, Clinical and Experimental Research
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...
February 28, 2018: Pulmonary Pharmacology & Therapeutics
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
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
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...
February 21, 2018: Journal of Anesthesia
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
L McCreight, T B Stage, P Connelly, M Lonergan, F Nielsen, C Prehn, J Adamski, K Brosen, E R Pearson
AIMS: Metformin intolerance symptoms are gastrointestinal in nature, but the underlying mechanism is poorly understood. The aim of this study was to assess potential causes of metformin intolerance including: altered metformin uptake from the intestine; increased anaerobic glucose utilisation and subsequent lactate production; altered serotonin uptake; and altered bile acid pool. METHODS: This pharmacokinetic study recruited ten severely intolerant and ten tolerant individuals matched for age, sex and BMI...
February 19, 2018: Diabetes, Obesity & Metabolism
J M Zilberman
Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists...
January 28, 2018: Hipertensión y Riesgo Vascular
Mie Kunio, Gee Wong, Peter M Markham, Elazer R Edelman
Sex-related differences have been noted in cardiovascular anatomy, pathophysiology, and treatment responses, yet we continued to drive evaluation of vascular device development in animal models without consideration of animal sex. We aimed to understand sex-related differences in the vascular responses to stent implantation by analyzing the pooled data of endovascular interventions in 164 Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation, 68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES implantation)...
2018: PloS One
Robert Miller, Jan-Georg Wojtyniak, Lisa J Weckesser, Nina C Alexander, Veronika Engert, Thorsten Lehr
This article seeks to address the prevailing issue of how to measure specific process components of psychobiological stress responses. Particularly the change of cortisol secretion due to stress exposure has been discussed as an endophenotype of many psychosomatic health outcomes. To assess its process components, a large variety of non-compartmental parameters (i.e., composite measures of substance concentrations at different points in time) like the area under the concentration-time curve (AUC) are commonly utilized...
December 29, 2017: Psychoneuroendocrinology
Sreeneeranj Kasichayanula, Anita Grover, Maurice G Emery, Megan A Gibbs, Ransi Somaratne, Scott M Wasserman, John P Gibbs
Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2 that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly through saturable binding to PCSK9 at lower concentrations and a nonsaturable proteolytic pathway at higher concentrations. The effective half-life of evolocumab is 11-17 days...
January 20, 2018: Clinical Pharmacokinetics
Divi Cornec, Brian F Kabat, John R Mills, Melissa Cheu, Amber M Hummel, Darrell R Schroeder, Matthew D Cascino, Paul Brunetta, David L Murray, Melissa R Snyder, Fernando Fervenza, Gary S Hoffman, Cees G M Kallenberg, Carol A Langford, Peter A Merkel, Paul A Monach, Philip Seo, Robert F Spiera, E William St Clair, John H Stone, David R Barnidge, Ulrich Specks
Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes. Methods: This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by computing the trapezoidal area under the curve. We explored potential determinants of the PK-RTX, and analysed its association with clinical outcomes: achievement of remission at 6 months, duration of B-cell depletion and time to relapse in patients who achieved complete remission...
January 10, 2018: Rheumatology
Vidya Chidambaran, Anurag Tewari, Mohamed Mahmoud
PURPOSE: Anesthetic management of obese pediatric patients is challenging. With increasing prevalence of childhood obesity, more severely obese children with comorbidities present for surgery every day. The purpose of this review is to provide an up-to-date comprehensive narrative review on the impact of pathophysiological changes imposed by pediatric obesity on the perioperative management of obese children, especially drug dosing. This knowledge is necessary to provide safe delivery of anesthesia for severely obese children...
December 21, 2017: Journal of Clinical Anesthesia
W Zhong, Y Zhang, M-Z Zhang, X-H Huang, Y Li, R Li, Q-W Liu
WHAT IS KNOWN AND OBJECTIVE: The primary objective of this study was to compare the pharmacokinetics of dexmedetomidine in patients with end-stage renal failure and secondary hyperparathyroidism with those in normal individuals. METHOD: Fifteen patients with end-stage renal failure and secondary hyperparathyroidism (Renal-failure Group) and 8 patients with normal renal and parathyroid gland function (Control Group) received intravenous 0.6 μg/kg dexmedetomidine for 10 minutes before anaesthesia induction...
December 16, 2017: Journal of Clinical Pharmacy and Therapeutics
C Bon, P L Toutain, D Concordet, R Gehring, T Martin-Jimenez, J Smith, L Pelligand, M Martinez, T Whittem, J E Riviere, J P Mochel
A common feature of human and veterinary pharmacokinetics is the importance of identifying and quantifying the key determinants of between-patient variability in drug disposition and effects. Some of these attributes are already well known to the field of human pharmacology such as bodyweight, age, or sex, while others are more specific to veterinary medicine, such as species, breed, and social behavior. Identification of these attributes has the potential to allow a better and more tailored use of therapeutic drugs both in companion and food-producing animals...
April 2018: Journal of Veterinary Pharmacology and Therapeutics
Szeman Ruby Chan, Kelley Salem, Justin Jeffery, Ginny L Powers, Yongjun Yan, Kooresh I Shoghi, Aparna M Mahajan, Amy M Fowler
The study objective was to investigate whether sex influences 3'-deoxy-3'-[18 F]fluorothymidine (18 F-FLT) uptake and tissue distribution in mouse models of cancer. Methods: 18 F-FLT biodistribution was measured in three strains of male and female mice (129S6/SvEv, athymic nude, and BALB/c).18 F-Fluoro-2-deoxy-2-D-glucose (18 F-FDG) biodistribution was performed for comparison.18 F-FLT uptake was also measured in female 129S6/SvEv mice bearing estrogen-dependent SSM3 mouse mammary tumors, male athymic nude mice bearing androgen-dependent CWR22 prostate cancer xenografts, and male and female athymic nude mice bearing estrogen-independent MDA-MB-231 human breast cancer xenografts...
December 7, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Wenge Chen, Yingying Xiao, Jianzhong Chen, Jian Liu, Jingwei Shao, Tao Li, Yewei Zhu, Ji Ma, Yu Gao, Jichuang Wang, Jianguo Xu, Yusheng Lu, Lee Jia
Metapristone is the primary metabolite of the abortifacient mifepristone (RU486), and is being developed as a safe and effective cancer metastatic chemopreventive agent for both sexes. Here, we systematically investigated the sex-related pharmacokinetics of metapristone in both rats and dogs, and explored the related mechanisms of actions. Administration of metapristone to rats and dogs showed that plasma concentrations of metapristone (AUC, Cmax ) were significantly higher in female dogs and rats than in males...
December 7, 2017: Scientific Reports
Islam R Younis, Mariam A Ahmed, Kenneth D Burman, Offie P Soldin, Jacqueline Jonklaas
BACKGROUND: This study sought to determine whether levothyroxine pharmacokinetics (PKs) are affected by age, weight, and sex. METHODS: A PK study was performed after administration of a tracer dose of carbon-13-labeled LT4 (13 C-LT4). The study was conducted at an academic medical center. Adults of any age being treated with levothyroxine for hypothyroidism were enrolled in the study. A single dose of13 C-LT4 was administered. Eighteen serial plasma samples were collected...
January 2018: Thyroid: Official Journal of the American Thyroid Association
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"