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Drug dosing in obesity

Katie B Tellor, Steffany N Nguyen, Amanda C Bultas, Anastasia L Armbruster, Nicholas A Greenwald, Abigail M Yancey
BACKGROUND: Despite well established empiric dose adjustments for drug and disease-state interactions, the impact of body mass index (BM) on warfarin remains unclear. The objective of this study is to evaluate warfarin requirements in hospitalized patients, stratified by BMI. METHODS: This retrospective review included two cohorts of patients: cohort A (patients admitted with a therapeutic international normalized ratio (INR)) and cohort B (newly initiated on warfarin during hospitalization)...
June 1, 2018: Therapeutic Advances in Cardiovascular Disease
Benjamin Bouyer, Annie Rudnichi, Rosemary Dray-Spira, Mahmoud Zureik, Joël Coste
BACKGROUND: Post-operative venous thromboembolism (VTE) is a severe complication, the risk of which after lumbar spine surgery (LBS) is not precisely known. OBJECTIVE: To estimate the incidence of VTE after LBS and to identify individual and surgical risk factors. METHODS: All patients over the age of 18 years who underwent LBS in France between 2009 and 2014 were identified. Among 477,024 patients screened, exclusions concerned recent VTE or surgery and multiple surgeries during the same hospital stay...
June 12, 2018: Journal of Thrombosis and Haemostasis: JTH
Hyejin Lee, Hua Li, Minson Kweon, Youngsook Choi, Min Jung Kim, Jae-Ha Ryu
We isolated isobavachalcone (IBC) from Angelica keiskei (AK) as an anti-obesity component. IBC dose-dependently inhibited 3T3-L1 adipocyte differentiation by down-regulating adipogenic factors. At the mitotic clonal expansion stage (MCE), IBC caused cell cycle arrest in G0/G1 with decreased expression of cell cycle-regulating proteins. IBC also inhibited autophagic flux by inducing intracellular accumulation of LC3B and SQSTM1/p62 proteins while decreasing expression levels of regulating factors for autophagy initiation...
June 6, 2018: International Journal of Molecular Sciences
Linong Ji, Zhengnan Gao, Bimin Shi, Rongwen Bian, Fuzai Yin, Wuyan Pang, Hong Gao, Nan Cui
BACKGROUND: Treatment with basal insulin in Chinese populations is currently sub-optimal, with delayed initiation of insulin treatment and inadequate dose titration. Increasing the initial dose of insulin may be a practicable and effective solution to the problem of titration. A higher initial dose will be helpful for patients to achieve the blood glucose target and improve treatment satisfaction and compliance as well require fewer steps to titrate. Considering that overweight and obese patients usually require higher insulin doses because of insulin resistance, a higher initial dose of the basal insulin is feasible in overweight and obese patients with type 2 diabetes...
June 5, 2018: Advances in Therapy
Anthony J Viera
Resistant hypertension is a blood pressure (BP) level that remains above the goal level despite adherence to at least three appropriately dosed antihypertensive drugs of different classes, one of which is a diuretic. Evaluation of suspected resistant hypertension starts with confirming adherence to the drug regimen. White coat hypertension should be ruled out with out-of-office BP level measurements, ideally using 24-hour ambulatory BP monitoring. Obesity, significant alcohol intake, and interfering drugs and other substances can contribute to resistant hypertension...
June 2018: FP Essentials
A Heetun, R I Cutress, E R Copson
High BMI is associated with an increased risk of breast cancer in post-menopausal women but poorer outcomes in all age groups. The underlying mechanism is likely to be multi-factorial. Patients with a high BMI may present later due to body habitus. Some studies have also indicated an increased incidence of biologically adverse features, including a higher frequency of oestrogen receptor (ER negative) tumours, in obese patients. Obese patients have a higher frequency of surgical complications, potentially delaying systemic therapies, and reports suggest that chemotherapy and endocrine therapy are less effective in patients with BMI ≥30 kg/m2...
June 4, 2018: Proceedings of the Nutrition Society
David J Greenblatt, Jerold S Harmatz, Michael J Ryan, Christina R Chow
PURPOSE/BACKGROUND: The antipsychotic agent lurasidone (Latuda®) is metabolized by Cytochrome P450-3A (CYP3A) enzymes. Coadministration with strong CYP3A inhibitors (such as ketoconazole, posaconazole, and ritonavir) is contraindicated due to the risk of sedation and movement disorders from high levels of lurasidone. This study evaluated the time-course of recovery from the posaconazole drug interaction, and the effect of obesity on the recovery process. METHODS/PROCEDURES: Healthy normal-weight volunteers (n = 11, mean body mass index, BMI, = 23...
May 30, 2018: Journal of Clinical Psychopharmacology
Linda Tahaineh, Sahar M Edaily, Shadi F Gharaibeh
Objectives: To evaluate the degree of anticoagulation achieved with different enoxaparin dosing regimens used in obese and morbidly obese patients in a hospital setting in Jordan. Methods: All obese adult patients who were prescribed enoxaparin for various indications were invited to participate in the study. The anti-factor Xa (anti-Xa) level was checked once after 4-6 hours of the third or fourth dose of enoxaparin (at steady state). Patients were followed daily to evaluate drug efficacy and safety through their hospital course...
2018: Clinical Pharmacology: Advances and Applications
Yoon Young Cho, Min Jin Kang, Soo Kyoung Kim, Junghwa Jung, Jong Ryeal Hahm, Tae Hyuk Kim, Joo Young Nam, Byung-Wan Lee, Yong-Ho Lee, Jae Hoon Chung, Sun Ok Song, Sun Wook Kim
BACKGROUND: Metformin, the most widely used drug for type 2 diabetes has recently attracted attention with regard to its anti-tumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development despite its anti-tumor effect in preclinical studies. METHODS: This was a retrospective cohort study using the Korean National Health Insurance claims database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence...
May 29, 2018: Thyroid: Official Journal of the American Thyroid Association
Magdalena Kotańska, Kamil J Kuder, Katarzyna Szczepańska, Jacek Sapa, Katarzyna Kieć-Kononowicz
The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances. Therefore, we studied the influence of pitolisant on body weight, water and sucrose intake as well as metabolic disturbances in the high-fat and high-sugar diet-induced obesity model in mice. To induce obesity, male CD-1 mice were fed a high-fat diet consisting of 40% fat blend for 14 weeks, water and 30% sucrose solution available ad libitum...
May 25, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Wei-Jia Luo, Ting-Yu Cheng, Keng-Ieng Wong, Woei-Horng Fang, Keng-Mao Liao, Yun-Ting Hsieh, Kang-Yi Su
Non-alcoholic fatty liver disease (NAFLD) is a problem in obese people caused by increasing intake of high-calorie food such as fructose implicated in the elevated prevalence. It is necessary to identify novel drugs to develop effective therapies. In this study, we combined LOPAC® (The Library of Pharmacologically Active Compounds) and High-Content screening to identify compounds that significantly reduced intracellular lipid droplets (LD) after high fat medium (HFM) treatment. Among 1280 compounds, we identified 239 compounds that reduced LD by >50%...
May 23, 2018: European Journal of Pharmaceutical Sciences
Fariba M Assadi-Porter, Hannah Reiland, Martina Sabatini, Leonardo Lorenzini, Vittoria Carnicelli, Micheal Rogowski, Ebru S Selen Alpergin, Marco Tonelli, Sandra Ghelardoni, Alessandro Saba, Riccardo Zucchi, Grazia Chiellini
Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways...
May 22, 2018: International Journal of Molecular Sciences
Lianjie Xiong, Z Kevin Lu, April Miller Quidley, Bebbyn S Alford, P Brandon Bookstaver
OBJECTIVES: The study compared estimated creatinine clearance (eCrCl) between the Cockcroft-Gault (CG) equation and the Jelliffe, Chiou, and Brater equations designed for estimation in dynamic renal function and resulting antimicrobial dosing concordance of five antimicrobials (cefepime, meropenem, piperacillin/tazobactam, vancomycin, and fluconazole) commonly used in the intensive care unit (ICU). METHODS: Electronic medical records were used to identify the target patient population...
May 2018: Southern Medical Journal
Ahmed Mediani, Faridah Abas, M Maulidiani, Azliana Abu Bakar Sajak, Alfi Khatib, Chin Ping Tan, Intan Safinar Ismail, Khozirah Shaari, Amin Ismail, N H Lajis
Diabetes mellitus (DM) is a chronic disease that can affect metabolism of glucose and other metabolites. In this study, the normal- and obese-diabetic rats were compared to understand the diabetes disorders of type 1 and 2 diabetes mellitus. This was done by evaluating their urine metabolites using proton nuclear magnetic resonance (1 H NMR)-based metabolomics and comparing with controls at different time points, considering the induction periods of obesity and diabetes. The biochemical parameters of the serum were also investigated...
May 15, 2018: Journal of Physiology and Biochemistry
Christina R Chow, Jerold S Harmatz, Michael J Ryan, David J Greenblatt
The antianginal agent ranolazine (Ranexa®) is metabolized primarily by cytochrome P450-3A (CYP3A) enzymes. Coadministration with strong CYP3A inhibitors, such as ketoconazole and posaconazole, is contraindicated due to risk of QT prolongation from high levels of ranolazine. This study evaluated the time course of recovery from the posaconazole drug interaction in normal-weight and otherwise healthy obese subjects. Subjects received single doses of ranolazine in the baseline control condition, again during coadministration of posaconazole, and at 4 additional time points during the 2 weeks after posaconazole discontinuation...
May 11, 2018: Journal of Clinical Pharmacology
A Mucha
Diabetes mellitus type 2 is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and relative insulin deficiency. There are rare cases when even higher doses of insulin are insufficient to control the values of glycemia. The insulin resistance can be mild, moderate or severe. Authors present a clinical case report of a mild insulin resistance in a 46 year-old female patient with clinical symptoms of insulin resistance (including obesity), treated for seven years with oral antidiabetic drugs...
April 2018: Georgian Medical News
Christina Gade, Hanne R Christensen, Kim P Dalhoff, Jens Christian Holm, Helle Holst
Obesity can affect the pharmacokinetics of most drugs, which may result in under- or overdosing if traditional pediatric dosing strategies are used. To investigate currently applied dosage strategies in children with overweight or obesity (overweight/obesity), in a clinical treatment facility. In particular, whether dosing guidelines were available and metrics of body size applied. A retrospective cohort study of 200 patients admitted to the Danish Children's Obesity Clinic. Data were collected from 2007 to 2015...
June 2018: Pharmacology Research & Perspectives
Mary Banoub, Melanie S Curless, Janessa M Smith, Andrew S Jarrell, Sara E Cosgrove, Clare Rock, Edina Avdic
BACKGROUND: Clinical practice guidelines recommend a 2-g dose of cefotetan and cefoxitin for surgical prophylaxis. Pharmacokinetic data suggest benefit from higher cefotetan and cefoxitin dosing in obese patients. However, clinical studies examining higher dosing strategies in this at-risk population are lacking. The purpose of this study was to determine whether 3 g of cefotetan or cefoxitin administered pre-operatively for patients who weigh 120 kg or more is associated with a lower proportion of surgical site infection (SSI) compared with 2 g...
May 2, 2018: Surgical Infections
Roeland E Wasmann, Rob Ter Heine, Eric P van Dongen, David M Burger, Vincent J Lempers, Catherijne A Knibbe, Roger J Brüggemann
In 2025, approximately one out of five adults will be obese. Physiological changes associated with obesity have shown to influence the pharmacokinetics of drugs. Anidulafungin is frequently used in critically ill patients and to achieve optimal efficacy it is essential that its dose is appropriate for each patients' characteristics. We combined data from obese subjects with data from normal-weight subjects and determined an optimal dosing regimen for obese patients by population-PK modeling.Twenty adults, of which twelve were normal-weight healthy subjects (median weight 67...
April 30, 2018: Antimicrobial Agents and Chemotherapy
Tianjiao Zhou, Chengzhen Meng, Pingli He
BACKGROUND: Soy isoflavones, such as genistein and daidzein, are bioflavonoids found in soy products that are able to interact with various hormones such as estrogen. Epidemiological studies reveal a proper level of isoflavones in diet can prevent many diseases like cancers or diabetes. Therefore, it is important to study the biotransformation and xenobiotic metabolism of soy isoflavones. METHODS: A systematic review of published studies was carried out to investigate the characterization of isoflavones and their metabolites, sample pretreatment and quantitative analysis of isoflavones, and the influence of soy isoflavones on drug and xenobiotic metabolism...
April 27, 2018: Current Drug Metabolism
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