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Drug dosing in obesity

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https://www.readbyqxmd.com/read/29669668/pharmacokinetics-of-intranasal-mometasone-in-the-fixed-dose-combination-gsp301-versus-two-monotherapy-intranasal-mometasone-formulations
#1
Piyush Patel, Anne Marie Salapatek, Ravi S Talluri, Sudeesh K Tantry
BACKGROUND: GSP301 is a fixed-dose combination (FDC) of the antihistamine olopatadine hydrochloride and the corticosteroid mometasone furoate developed as a single nasal spray (NS). OBJECTIVE: To assess the relative bioavailability of mometasone administered as GSP301 FDC versus two mometasone monotherapy NS formulations. METHODS: In this single-dose, open-label, crossover study, healthy adults (age range, 18-65 years) were randomized equally to one of six treatment sequences for three 72-hour treatment periods with GSP301 (olopatadine 665 μg-mometasone 50 μg), the mometasone furoate monotherapy component of GSP301 (MF-sponsor, 50 μg), and U...
May 1, 2018: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/29665045/high-body-mass-index-is-associated-with-increased-risk-of-treatment-failure-and-surgery-in-biologic-treated-patients-with-ulcerative-colitis
#2
S Kurnool, N H Nguyen, J Proudfoot, P S Dulai, B S Boland, N Vande Casteele, E Evans, E L Grunvald, A Zarrinpar, W J Sandborn, S Singh
BACKGROUND: Though pharmacokinetic studies suggest accelerated biologic drug clearance with increasing body weight, evidence of obesity's impact on clinical outcomes in biologic-treated patients with ulcerative colitis (UC) is inconsistent. AIMS: To evaluate the impact of obesity on real world response to biological therapy in patients with UC. METHODS: In a single-centre retrospective cohort study between 2011-2016 of biologic-treated patients with UC, we evaluated treatment response by baseline body mass index (BMI)...
April 17, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29660397/a-pharmacology-guided-approach-for-setting-limits-on-product-related-impurities-for-bispecific-antibody-manufacturing
#3
Sharmila Rajan, Junichiro Sonoda, Timothy Tully, Ambrose J Williams, Feng Yang, Frank Macchi, Terry Hudson, Mark Z Chen, Shannon Liu, Nicole Valle, Kyra Cowan, Thomas Gelzleichter
INTRODUCTION: bFKB1 is a humanized bispecific IgG1 antibody, created by conjoining an anti-Fibroblast Growth Factor Receptor 1 (FGFR1) half-antibody to an anti-Klothoβ (KLB) half-antibody, using the knobs-into-holes strategy. bFKB1 acts as a highly selective agonist for the FGFR1/KLB receptor complex and is intended to ameliorate obesity-associated metabolic defects by mimicking the activity of the hormone FGF21. An important aspect of the biologics product manufacturing process is to establish meaningful product specifications regarding the tolerable levels of impurities that copurify with the drug product...
April 13, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29656496/fast-and-sensitive-hplc-uv-method-for-cefazolin-quantification-in-plasma-and-subcutaneous-tissue-microdialysate-of-humans-and-rodents-applied-to-pharmacokinetic-studies-in-obese-individuals
#4
Eduardo Celia Palma, João Victor Laureano, Bibiana Verlindo de Araújo, Nelson Guardiola Meinhardt, Airton Tetelbom Stein, Teresa Dalla Costa
Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals due to alterations on drug´s tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need of cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm...
April 14, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29655677/an-in-vitro-and-in-vivo-study-of-a-4-herb-formula-on-the-management-of-diet-induced-metabolic-syndrome
#5
Elaine Wat, Yanping Wang, Ken Chan, Hon Wai Law, Chi Man Koon, Kit Man Lau, Ping Chung Leung, Choly Yan, Clara Bik San Lau
BACKGROUND: Metabolic syndrome is the cluster of risk factors that leads to increased episodes of cardiovascular disease (CVD). These risk factors include but are not limited to obesity, non-alcoholic fatty liver (NAFLD), dyslipidemia, and type 2 diabetes. Since the pathogenesis of metabolic syndrome has multiple metabolic origins, there is no single treatment for it. Pharmacological approaches consist of separate drugs which target at individual risk factors which pose various side effects...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29651435/which-kidney-transplant-recipients-can-benefit-from-the-initial-tacrolimus-dose-reduction
#6
Kinga Krzyżowska, Aureliusz Kolonko, Piotr Giza, Jerzy Chudek, Andrzej Więcek
Background: Observational data suggest that the fixed initial recommended tacrolimus (Tc) dosing (0.2 mg/kg/day) results in supratherapeutic drug levels in some patients during the early posttransplant period. The aim of the study was to analyze a wide panel of patient-related factors and their interactions which increase the risk for first Tc blood level > 15 ng/ml. Materials and Methods: We performed a retrospective analysis of 488 consecutive adult kidney transplant recipients who were initially treated with triple immunosuppressive regimen containing tacrolimus twice daily...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29624732/effect-of-a-5-ht2c-receptor-agonist-on-urethral-closure-mechanisms-in-female-rats
#7
Mifuka Ouchi, Takeya Kitta, Yukiko Kanno, Madoka Higuchi, Mio Togo, Kimihiko Moriya, Nobuo Shinohara
AIMS: The serotonin (5-HT2c) receptor is known to be involved in the mechanism of urethral closure in a model of stress incontinence. Lorcaserin (Belviq®) has received Food and Drug Administration approval for the treatment of obesity. However, it is unclear whether this selective 5-HT2c receptor agonist enhances urethral closure in stress urinary incontinence (SUI) models. Therefore, we investigated whether lorcaserin could enhance urethral closure in female rats with vaginal distention (VD)...
April 6, 2018: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29615083/therapeutic-potentials-of-quercetin-in-management-of-polycystic-ovarian-syndrome-using-letrozole-induced-rat-model-a-histological-and-a-biochemical-study
#8
Sarwat Jahan, Abira Abid, Sidra Khalid, Tayyaba Afsar, Qurat-Ul-Ain, Ghazala Shaheen, Ali Almajwal, Suhail Razak
BACKGROUND: PCOS is a leading endocrinopathy of young women instigating androgens elevation, insulin resistance, obesity, cardiometabolic and menstrual complications. The study investigated the effects of quercetin in a letrozole induced rat model of polycystic ovarian syndrome, which displayed both clinical and metabolic features as in PCOS women. METHODS: Female Sprague Dawley (SD) rats were divided into four groups; control group received aqueous solution of carboxymethyl (CMC 0...
April 3, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29609909/-why-is-the-morbidly-obese-patient-at-high-risk-of-anesthetic-complications
#9
Audrey De Jong, Daniel Verzilli, Marie Geniez, Gérald Chanques, David Nocca, Samir Jaber
Obesity is often associated with obstructive sleep apnea (OSA), which increases the risk of intraoperative and postoperative complications. The role of preoperative screening of OSA is crucial, with adequate management based on continuous positive pressure before, during and after surgery. The obese patient is at risk of postoperative complications: difficult airway management, acute respiratory failure following extubation due to atelectasis and airway obstruction, added to morphine overdosing. Optimal management of difficult mask ventilation and intubation, protective ventilation, combined to the reduction of sedatives and analgesics and the sitting position as soon as possible with a postoperative monitoring should decrease the occurrence of complications...
March 30, 2018: La Presse Médicale
https://www.readbyqxmd.com/read/29594677/monitoring-of-gentamicin-serum-concentrations-in-obstetrics-and-gynaecology-patients-in-namibia
#10
Bonifasius S Singu, Mwangana Mubita, Moses M Thikukutu, Josef K Mufenda, Shonag B McKenzie, Roger K Verbeeck
Background Therapeutic drug monitoring is frequently used to optimize the gentamicin dose. Objective The study investigated whether a 240 mg once daily standard dose achieves the recommended target serum gentamicin concentrations. Setting The prospective, observational study took place in the 2 major public hospitals in Namibia. Method Twenty-nine female patients receiving a standard dose (240 mg gentamicin once daily) participated in the study. Two blood samples were withdrawn to estimate gentamicin pharmacokinetic parameters...
March 28, 2018: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/29588201/promotive-effect-of-bofutsushosan-fangfengtongshengsan-on-lipid-and-cholesterol-excretion-in-feces-in-mice-treated-with-a-high-fat-diet
#11
Junji Akaki, Shiori Tachi, Naoki Nakamura, Tetsuya Arai, Hiroo Yamasaki, Makoto Inoue, Toshiaki Makino
ETHNOPHARMACOLOGICAL RELEVANCE: Bofutsushosan (fangfengtongshengsan in Chinese, BTS) is a formula in traditional Japanese Kampo medicine and Chinese medicine comprising 18 crude drugs that is used for treating obesity and metabolic syndrome. AIM OF THE STUDY: We evaluated the promotive effects of BTS on lipid and cholesterol elimination in mice. MATERIALS AND METHODS: Mice were reared with a high-fat diet containing boiled water extract of BTS for 30 days, and their biochemical parameters as well as the weight and lipid content of feces were measured...
March 24, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29582416/body-fat-reduction-without-cardiovascular-alteration-in-mice-under-oral-treatment-by-the-mao-inhibitor-phenelzine
#12
Christian Carpéné, Josep Mercader, Sophie Le Gonidec, Stéphane Schaak, Jeanne Mialet-Perez, Alexia Zakaroff-Girard, Jean Galitzky
BACKGROUND AND PURPOSE: Phenelzine is an antidepressant drug increasing the risk of hypertensive crisis when dietary tyramine is not restricted. However, this monoamine oxidase (MAO) inhibitor is known to inhibit other enzymes not limited to the nervous system. We studied whether its antiadipogenic and antilipogenic effects in cultured adipocytes could contribute to a mitigation of fattening without unwanted hypertensive or cardiovascular effects. EXPERIMENTAL APPROACH: Mice were fed a standard chow and subjected to a 0...
March 26, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29574565/atorvastatin-decreases-steroid-production-in-h295r-cells-and-in-major-endocrine-tissues-of-male-rats
#13
Cecilie Hurup Munkboel, Michelle L K Baake, Bjarne Styrishave
Obesity is increasing worldwide, and since obesity is associated with dyslipidemia, the consumption of cholesterol-lowering pharmaceuticals has increased. The aim of this study was therefore to study potential endocrine disrupting effects of one of the world's most frequently prescribed drugs, the cholesterol-lowering drug, atorvastatin (ATO) in vitro using the H295R steroidogenesis assay and in vivo using male Sprague-Dawley rats. We analyzed all major steroids in the mammalian steroidogenesis using liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
March 24, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29567865/indomethacin-enhanced-brown-fat-activity
#14
Lei Hao, Jamie Kearns, Sheyenne Scott, Dayong Wu, Sean D Kodani, Christophe Morisseau, Bruce D Hammock, Xiaocun Sun, Shu Wang, Ling Zhao
Indomethacin, a non-steroidal anti-inflammatory drug, has been shown to induce white adipocyte differentiation; however, its roles in brown adipocyte differentiation, and activation in brown adipose tissue (BAT) and obesity are unknown. To address this issue, we treated mouse pre-brown cells with different doses of indomethacin, and delivered indomethacin to interscapular BAT (iBAT) of obese mice using implanted osmotic pumps. Indomethacin dose-dependently increased brown adipocyte differentiation, and upregulated both mRNA and protein expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor (PPAR) gamma (γ) coactivator 1-alpha...
March 22, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29547895/gout-state-of-the-art-after-a-decade-of-developments
#15
Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
https://www.readbyqxmd.com/read/29534980/effects-of-paullinia-cupana-extract-on-lamotrigine-pharmacokinetics-in-rats-an-herb-drug-interaction-on-the-gastrointestinal-tract-with-potential-clinical-impact
#16
Sandra Ventura, Márcio Rodrigues, Amílcar Falcão, Gilberto Alves
Paullinia cupana-containing preparations are being consumed worldwide for weight reduction. As obesity and epilepsy are common comorbidities and lamotrigine (LTG) is a broad-spectrum antiepileptic drug, it is likely to find epilepsy patients taking P. cupana and LTG simultaneously. Thus, this work aimed to investigate the potential interaction between P. cupana extract and LTG in rats. In a study, rats were orally co-administered with a single-dose of P. cupana extract (821 mg/kg) and LTG (10 mg/kg). In another study, rats were orally pre-treated for 14 days with P...
March 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29528251/clinical-safety-and-tolerability-of-tedizolid-phosphate-in-the-treatment-of-acute-bacterial-skin-and-skin-structure-infections
#17
Cathy Hardalo, Thomas P Lodise, Monique Bidell, Shawn Flanagan, Carisa De Anda, Steven Anuskiewicz, Philippe Prokocimer
BACKGROUND: We evaluated safety and tolerability of tedizolid phosphate at the 200-mg once-daily dose approved for 6-day treatment of skin and skin-structure infections. RESEARCH DESIGN AND METHODS: Clinical adverse event (AE) and laboratory data were pooled across completed clinical studies (13 phase 1, two phase 2, and two phase 3), for all participants who received ≥1 dose of tedizolid 200 mg, linezolid 600 mg (phase 3 only), or placebo (phase 1 only). RESULTS: 1280 participants received tedizolid (phase 1: n = 355; phase 2/3: n = 925)...
March 12, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29512306/preventing-muscle-wasting-by-osteoporosis-drug-alendronate-in-vitro-and-in-myopathy-models-via-sirtuin-3-down-regulation
#18
Hsien-Chun Chiu, Chen-Yuan Chiu, Rong-Sen Yang, Ding-Cheng Chan, Shing-Hwa Liu, Chih-Kang Chiang
BACKGROUND: A global consensus on the loss of skeletal muscle mass and function in humans refers as sarcopenia and cachexia including diabetes, obesity, renal failure, and osteoporosis. Despite a current improvement of sarcopenia or cachexia with exercise training and supportive therapies, alternative and specific managements are needed to discover for whom are unable or unwilling to embark on these treatments. Alendronate is a widely used drug for osteoporosis in the elderly and postmenopausal women...
March 6, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29506228/sarcopenic-obesity-hidden-muscle-wasting-and-its-impact-for-survival-and-complications-of-cancer-therapy
#19
V E Baracos, L Arribas
Body composition, defined as the proportions and distribution of lean and fat tissues in the human body, is an emergent theme in clinical oncology. Severe muscle depletion (sarcopenia) is most easily overlooked in obese patients; the advent of secondary analysis of oncologic images provides a precise and specific assessment of sarcopenia. Here, we review the definitions, prevalence and clinical implications of sarcopenic obesity (SO) in medical and surgical oncology. Reported prevalence of SO varies due to the heterogeneity in the definitions and the variability in the cut points used to define low muscle mass and high fat mass...
February 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29501602/prophylactic-cefazolin-concentrations-in-morbidly-obese-patients-undergoing-sleeve-gastrectomy-do-we-achieve-targets
#20
Matthieu Grégoire, Romain Dumont, Ludovic Ronchi, Jean-Baptiste Woillard, Vincent Atthar, Eric Letessier, Raphaël Cinotti, Antoine Roquilly, Guillaume Deslandes, Pascale Jolliet, Karim Asehnoune, Eric Dailly
Morbid obesity is known to increase the risk of surgical site infections. Optimal concentrations of prophylactic antibacterial drugs are required. Using Monte Carlo simulations, the aim of this work was to build a population pharmacokinetics model for a morbidly obese population to assess a 4000-mg dose of cefazolin recommended by the guidelines and to propose new administration schemes. One hundred and seventeen morbidly obese patients (mean body mass index, 46.95 kg/m2 ) received 4000 mg of cefazolin intravenously before sleeve gastrectomy...
March 1, 2018: International Journal of Antimicrobial Agents
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