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Drug dosing in obesity

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https://www.readbyqxmd.com/read/29232311/lithium-colchicine-a-potential-strategy-to-reduce-pro-inflammatory-effects-of-lithium-treatment
#1
John J Mooney, Roscoe O Brady
PURPOSE: Rosenblat and McIntyre (Acta Psychiatr Scand. 2015;132: 180-191) propose that immune disorders are important mediators between bipolar disorders and medical comorbidities. Rosenblat et al (Bipolar Disord. 2016;18:89-101) present a meta-analysis showing that adjunctive anti-inflammatory agents could evoke moderate antidepressant responses in bipolar disorders. We propose using the anti-inflammatory drug colchicine to improve the long-term safety and efficacy of lithium treatment for bipolar disorders...
December 11, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29217539/inhibition-of-cocaine-and-3-4-methylenedioxypyrovalerone-mdpv-self-administration-by-lorcaserin-is-mediated-by-5-ht2c-receptors-in-rats
#2
Brenda M Gannon, Agnieszka Sulima, Kenner C Rice, Gregory T Collins
Lorcaserin is a serotonin (5-HT)2C receptor-preferring agonist approved by the US Food and Drug Administration to treat obesity. Lorcaserin has been shown to decrease cocaine self-administration in rats and monkeys. Although this effect is partially inhibited by a 5-HT2C receptor antagonist (SB 242084), lorcaserin also has effects at 5-HT2A and 5-HT1A receptors and the relative contribution of these receptors to its anti-cocaine effects has not been investigated. The goals of this study were to determine: (1) the potency and effectiveness of lorcaserin to decrease self-administration of cocaine and 3,4-methylenedioxypyrovalerone (MDPV), a common "bath salts" constituent; and (2) the receptor(s) mediating the effects of lorcaserin on cocaine and MDPV self-administration...
December 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29211322/perivascular-adipose-tissue-and-the-dynamic-regulation-of-kv-7-and-kir-channels-implications-to-resistant-hypertension
#3
Maik Gollasch, Donald G Welsh, Rudolf Schubert
Resistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive drugs at adequate doses. Resistant hypertension is an increasingly common clinical problem in older age, obesity, diabetes, sleep apnea, and chronic kidney disease. Although the direct vasodilator minoxidil was introduced in the early 1970s, only recently has this drug been shown to be particularly effective in a subgroup of patients with treatment-resistant or uncontrolled hypertension...
December 6, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29174039/lavatera-critica-a-green-leafy-vegetable-controls-high-fat-diet-induced-hepatic-lipid-accumulation-and-oxidative-stress-through-the-regulation-of-lipogenesis-and-lipolysis-genes
#4
Chinnadurai Veeramani, Mohammed A Alsaif, Khalid S Al-Numair
BACKGROUND: Lipid accumulation is the most vital risk factor for inducing nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. Thus, the development of novel drugs is urgently needed to control obesity related diseases. OBJECTIVE: Here, we investigated the protective role of Lavatera critica (LC), a green vegetable, in male C57BL/6J mice fed with high fat (HF) diet for 10 weeks to induce hepatic lipid accumulation and oxidative cellular damage. RESULTS: After oral administration of chloroform (CFLC), ethyl acetate (EFLC), or methanol (MFLC) fractions of Lavatera critica to the HF group, EALC alone significantly reduced the activities of hepatic markers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST); moreover, the results showed that 50 mg/kg dose has the maximum activity...
November 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29173979/-dose-adaptation-of-the-drugs-used-for-hematopoietic-stem-cell-transplantation-in-patients-with-comorbidity-obesity-chronic-renal-disease-or-hepatopathy-guidelines-from-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#5
Nicolas Simon, Valérie Coiteux, Bénédicte Bruno, Sophie Taque, Amandine Charbonnier, Laetitia Souchet, Laure Vincent, Ibrahim Yakoub-Agha, Yves Chalandon
In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th Allogeneic Stem Cell Transplantation Clinical Practices Harmonization Workshop Series. Our work group focused on chemotherapy drug dose adaptation for hematopoietic stem cell transplantation patients presenting a comorbidity. The purpose of this workshop was to provide recommendations on chemotherapy drug dose adaptation for patient populations receiving hematopoietic stem cell transplantation who also had the following comorbidities: obesity, chronic kidney disease and hepatopathy...
November 22, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29173794/drug-dosing-in-obese-children-challenges-and-evidence-based-strategies
#6
REVIEW
Ye Xiong, Tsuyoshi Fukuda, Catherijne A J Knibbe, Alexander A Vinks
With the alarming increase of obesity in children, pediatricians are increasingly being confronted with difficult dosing decisions. Many drug labels do not provide specific dosing instructions for children who are obese. In this article, we describe the physiologic parameters altered by obesity and their influences on drug disposition and effect. We review the principles of allometry, and the key pharmacokinetic parameters that can be used to derive age appropriate dosing regimens. Last, we illustrate how appropriate weight descriptors can be selected, and how important PK parameters can be extrapolated for dosing in obese children when pediatric pharmacokinetic information is available...
December 2017: Pediatric Clinics of North America
https://www.readbyqxmd.com/read/29170989/modeling-energy-intake-and-body-weight-effects-of-a-long-acting-amylin-analogue
#7
Annika Brings, Jens Markus Borghardt, Jolanta Skarbaliene, Tamara Baader-Pagler, Maria A Deryabina, Wolfgang Rist, Stefan Scheuerer
The inhibitory effect of anti-obesity drugs on energy intake (EI) is counter-acted by feedback regulation of the appetite control circuit leading to drug tolerance. This complicates the design and interpretation of EI studies in rodents that are used for anti-obesity drug development. Here, we investigated a synthetic long-acting analogue of the appetite-suppressing peptide hormone amylin (LAMY) in lean and diet-induced obese (DIO) rats. EI and body weight (BW) were measured daily and LAMY concentrations in plasma were assessed using defined time points following subcutaneous administration of the LAMY at different dosing regimens...
November 23, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29164831/udenafil-a-phosphodiesterase-5-inhibitor-reduces-body-weight-in-high-fat-fed-mice
#8
Seong Yul Ryu, Yoon Jung Choi, So Young Park, Jong Yeon Kim, Yong Dae Kim, Yong Woon Kim
PURPOSE: High-fat (HF) feeding induces hypothalamic leptin resistance via the activation of toll-like receptor 4 (TLR4). TLR4 deficiency confers resistance to diet-induced obesity. Udenafil, an anti-impotence drug, inhibits TLR4 in airway epithelial cells in vitro. In this study, we evaluated whether udenafil suppressed the hypothalamic expression of TLR4 and reduced body weight. MATERIALS AND METHODS: The hypothalamic expression of TLR4, phosphodiesterase 5 (PDE5), nuclear factor-κB (NF-κB), and myeloid differentiation primary response gene 88 (Myd88) was analyzed by real-time polymerase chain reaction after treating mice for 2 days with udenafil (0, 12, 120, or 600 μg/d)...
November 16, 2017: World Journal of Men's Health
https://www.readbyqxmd.com/read/29133606/effects-of-bariatric-surgery-in-obese-patients-with-hypertension-the-gateway-randomized-trial-gastric-bypass-to-treat-obese-patients-with-steady-hypertension
#9
Carlos Aurelio Schiavon, Angela Cristine Bersch-Ferreira, Eliana Vieira Santucci, Juliana Dantas Oliveira, Camila Ragne Torreglosa, Priscila Torres Bueno, Julia Caldas Frayha, Renato Nakagawa Santos, Lucas Petri Damian, Patricia Malvina Noujaim, Helio Halpern, Frederico L J Monteiro, Ricardo Vitor Cohen, Carlos H Uchoa, Marcio Gonçalves de Souza, Celso Amodeo, Luiz Bortolotto, Dimas Ikeoka, Luciano F Drager, Alexandre Biasi Cavalcanti, Otavio Berwanger
BACKGROUND : Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed. METHODS : In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m(2) Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29131442/increased-rates-of-atrial-fibrillation-recurrence-following-pulmonary-vein-isolation-in-overweight-and-obese-patients
#10
Bhradeev Sivasambu, Muhammad A Balouch, Tarek Zghaib, Rizma J Bajwa, Jonathan Chrispin, Ronald D Berger, Hiroshi Ashikaga, Saman Nazarian, Joseph E Marine, Hugh Calkins, David D Spragg
INTRODUCTION: Catheter ablation is common for patients with symptomatic, drug-refractory atrial fibrillation (AF). Obesity is a known risk factor for incident AF. The impact of obesity on AF ablation outcomes is incompletely understood. We sought to determine the impact of elevated body mass index (BMI) on pulmonary vein isolation (PVI) procedural outcomes and associated complications. METHODS AND RESULTS: We evaluated patients undergoing PVI from 2001 to 2015, dividing them into four groups: normal weight (BMI ≥ 18...
November 13, 2017: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29131289/negative-predictors-of-treatment-success-in-outpatient-therapy-of-arterial-hypertension-in-poland-results-of-the-control-nt-observational-registry
#11
Krzysztof J Filipiak, Mariusz Tomaniak, Anna E Płatek, Filip M Szymański, Andrzej Tykarski
BACKGROUND: Identification of factors interfering with adequate control of arterial hypertension in the course of antihypertensive therapy is necessary to plan the strategy or reducing the incidence of cardiovascular disorders and optimize clinical practice guidelines. There have only been limited reliable studies describing the current status of hypertension treatment. AIM: The study objective was to conduct a screening assessment of the rate of uncontrolled hypertension among hypertensive patients coming to a routine follow-up visit, and to characterize patients with inadequate control of arterial hypertension in the aspect of their cardiovascular risk profile and therapeutic strategies used...
November 13, 2017: Kardiologia Polska
https://www.readbyqxmd.com/read/29119027/dosing-of-ertapenem-in-an-extreme-obesity-a-case-report-of-250%C3%A2-kg-patient
#12
Jana Lass, Kadri Tamme, Karin Kipper, Joel Starkopf
Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/29116785/a-positive-allosteric-modulator-of-the-serotonin-5-ht2c-receptor-for-obesity
#13
Javier García-Cárceles, Juan M Decara, Henar Vázquez-Villa, Ramón Rodríguez, Eva Codesido, Jacobo Cruces, José Brea, María I Loza, Francisco Alén, Joaquin Botta, Peter J McCormick, Juan A Ballesteros, Bellinda Benhamú, Fernando Rodríguez de Fonseca, María L López-Rodríguez
The 5-HT2CR agonist lorcaserin, clinically approved for the treatment of obesity, causes important side effects mainly related to subtype selectivity. In the search for 5-HT2CR allosteric modulators as safer antiobesity drugs, a chemical library from Vivia Biotech was screened using ExviTech platform. Structural modifications of identified hit VA240 in synthesized analogues 6-41 afforded compound 11 (N-[(1-benzyl-1H-indol-3-yl)methyl]pyridin-3-amine, VA012), which exhibited dose-dependent enhancement of serotonin efficacy, no significant off-target activities, and low binding competition with serotonin or other orthosteric ligands...
November 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29115454/mycoleptodonoides%C3%A2-aitchisonii-suppresses-asthma-via-th2-and-th1-cell-regulation-in-an-ovalbumin%C3%A2-induced-asthma-mouse-model
#14
Soon-Young Lee, Chun-Sik Bae, Ji-Hye Seo, Seung Sik Cho, Min-Suk Bae, Deuk-Sil Oh, Dae-Hun Park
Asthma is a chronic respiratory disease related to hyper‑responsiveness. The majority of patients suffer mild symptoms, however, some cases, especially in the young and the elderly, can lead to death by apnea. Mycoleptodonoides atichisonii (M. atichisonii) is an edible mushroom that has previously been reported to possess several bioactive properties, such as the synthesis of nerve growth factors, anti‑obesity effects and the ability to prevent cell death. In the current study, the authors evaluated the anti‑asthmatic effects of M...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109603/drug-dosing-in-obese-adults
#15
REVIEW
Michael Barras, Amy Legg
No abstract text is available yet for this article.
October 2017: Australian Prescriber
https://www.readbyqxmd.com/read/29105574/disagreement-in-estimates-of-kidney-function-for-drug-dosing-in-obese-inpatients
#16
Emily A Higdon, Lauren A Kimmons, Benjamin T Duhart, Joanna Q Hudson
BACKGROUND: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations are used to estimate kidney function. However, utility has been questioned in the obese population. OBJECTIVE: To evaluate differences in estimates of kidney function in obese patients and implications for drug dosing. METHODS: This was a retrospective study of adult inpatients with a body mass index ≥30 kg/m(2) and stable kidney function...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29103851/interaction-of-p-synephrine-on-the-pharmacodynamics-and-pharmacokinetics-of-gliclazide-in-animal-models
#17
Leela Krishna Vatsavai, Eswar Kumar Kilari
BACKGROUND: Type 2 diabetes is frequently seen in patients suffering from obesity. p-Synephrine and gliclazide are widely used medicines for the treatment of obesity and diabetes, respectively. Based on the relationship between obesity and diabetes, the present study was undertaken to determine the potential for herb-drug interactions between p-synephrine and gliclazide. METHODS: Influence of p-synephrine on the activity of gliclazide was determined by conducting single and multiple dose interaction studies in animal models...
November 3, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/29097359/customization-of-bilio-pancreatic-limb-length-to-modulate-and-sustain-anti-diabetic-effect-of-gastric-bypass-surgery
#18
Atanu Pal, David B Rhoads, Ali Tavakkoli
BACKGROUND: Although Roux-en-Y Gastric Bypass (RYGB) remains the most effective treatment for obesity and Type 2 Diabetes (T2D), many patients fail to achieve remission, or relapse. Increasing intestinal limb lengths of RYGB may improve outcomes, but the mechanistic basis for this remains unclear. We hypothesize Bilio-Pancreatic (BP) limb length modulates the anti-diabetic effect of RYGB. METHODS: Rats underwent RYGB with a 20-cm (RYGB-20cm) or 40-cm (RYGB-40cm) BP limb, and were compared to control animals...
November 2, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29090226/fifty-percent-ethanolic-extract-of-momordica-charantia-inhibits-adipogenesis-and-promotes-adipolysis-in-3t3-l1-pre-adipocyte-cells
#19
Chikkavadaragudi Ramachandra Shobha, Vishwanath Prashant, Prashant Akila, Rangaswamy Chandini, Maduvanahalli Nataraj Suma, Hattur Basavanagowdappa
BACKGROUND: Natural products have gained importance recently for the treatment of obesity and its complications, partly because of the side effects of modern drugs.Hence, we aimed to study and compare the effect of varying concentrations of Momordicacharantiaon adipogenesis and adipolysis using 3T3-L1 pre-adipocyte cell lines. METHODS: 3T3-L1 pre-adipocytes were procured from the National Center for Cell Sciences, Pune, and cultured in Dulbecco's Modified Eagle's Media (DMEM) supplemented with 20% fetal bovine serum (FBS) and 1 mM L-glutamine...
October 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29080937/population-pharmacokinetics-and-dosing-considerations-for-the-use-of-linezolid-in-overweight-and-obese-adult-patients
#20
Piergiorgio Cojutti, Manjunath P Pai, Federico Pea
BACKGROUND: Linezolid is an anti-Gram-positive antimicrobial agent used at a fixed dose of 600 mg every 12 h. OBJECTIVES: The objective of this study was to assess the population pharmacokinetics and pharmacodynamics of linezolid in a retrospective cohort of overweight and obese hospitalized patients. PATIENTS AND METHODS: Population pharmacokinetic and Monte Carlo simulations were conducted to assess the probability of target attainment (PTA) of an area under the concentration-time curve from time zero to 24 h (AUC24)/minimum inhibitory concentration (MIC) ratio > 100, defined as the pharmacodynamic target of efficacy, with incremental candidate dosages...
October 28, 2017: Clinical Pharmacokinetics
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