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Drug dosing in obesity

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https://www.readbyqxmd.com/read/29474345/opioid-related-genetic-polymorphisms-do-not-influence-postoperative-opioid-requirement-a-prospective-observational-study
#1
Frédéric Aubrun, Noël Zahr, Olivier Langeron, Nicolas Boccheciampe, Nathalie Cozic, Lisa Belin, Jean-Sebastien Hulot, Frederic Khiami, Bruno Riou
BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics...
February 22, 2018: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/29460396/lower-sperm-quality-and-testicular-and-epididymal-structural-impairment-in-adult-rats-exposed-to-rosuvastatin-during-prepuberty
#2
Gabriel Adan Araújo Leite, Marciana Sanabria, Marilia Martins Cavariani, Janete Aparecida Anselmo-Franci, Patrícia Fernanda Felipe Pinheiro, Raquel Fantin Domeniconi, Wilma De Grava Kempinas
The increase of obesity, bad eating habits and the lack of physical exercises are highly related to dyslipidemias. Rosuvastatin is a lipid-lowering drug and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to evaluate the reproductive adverse effects on sexual maturity due to rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were randomly formed with newly weaned rats: control, whose rats received saline solution 0...
February 19, 2018: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29431542/obesity-and-drug-pharmacology-a-review-of-the-influence-of-obesity-on-pharmacokinetic-and-pharmacodynamic-parameters
#3
Cornelis Smit, Sjoerd De Hoogd, Roger J M Brüggemann, Catherijne A J Knibbe
The rising prevalence of obesity confronts clinicians with dosing problems in the (extreme) overweight population. Obesity has a great impact on key organs that play a role in the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, however the ultimate impact of these changes on how to adapt the dose may not always be known. Areas covered: In this review, physiological changes associated with obesity are discussed. An overview is provided on the alterations in absorption, distribution, drug metabolism and clearance in (morbid) obesity focusing on general principles that can be extracted from pharmacokinetic studies...
February 12, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29409833/a-randomized-comparison-of-intravenous-sedation-using-a-dosing-algorithm-compared-to-standard-care-during-first-trimester-surgical-abortion
#4
Kari P Braaten, Richard D Urman, Rie Maurer, Jennifer Fortin, Alisa B Goldberg
OBJECTIVE: To compare the safety and efficacy of an algorithm for abortion intravenous sedation dosing (AAID) to standard dosing during first trimester surgical abortion. STUDY DESIGN: This was a randomized, single-blinded, controlled trial in which women undergoing first trimester surgical abortion received fentanyl and midazolam dosed either per an algorithm or clinic standard. Patient-level factors including weight, airway risk, anxiety, drug and alcohol use determined AAID doses...
January 31, 2018: Contraception
https://www.readbyqxmd.com/read/29407883/vasodilator-response-to-galvanic-current-stimulation-of-the-skin-accurately-detects-acetylsalicylic-acid-intake-a-study-in-400-vascular-patients
#5
Anne-Sophie Florczak, Samir Henni, Isabelle Signolet, Jean-François Hamel, Anne Humeau-Heurtier, Pascal Rousseau, Pierre Abraham
BACKGROUND AND AIMS: The first cause of low-dose acetylsalicylic-acid (ASA) inefficacy is poor adherence to treatment. No non-invasive technique is available to assess ASA intake. Current-induced vasodilation (CIV) was found abolished in healthy volunteers after low-dose ASA intake. We tested clinical characteristics, treatments, and comorbid conditions influencing CIV amplitude in vascular patients. METHODS: CIV was tested in 400 patients (277 males and 123 females, aged 65...
February 2, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29389444/obese-children-require-lower-doses-of-pantoprazole-than-nonobese-peers-to-achieve-equal-systemic-drug-exposures
#6
Valentina Shakhnovich, P Brian Smith, Jeffrey T Guptill, Laura P James, David N Collier, Huali Wu, Chad E Livingston, Jian Zhao, Gregory L Kearns
OBJECTIVE: To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials. STUDY DESIGN: A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula...
February 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29382592/the-obese-asthma-phenotype-in-children-an-exacerbating-situation
#7
Cristina Longo, Gillian Bartlett, Tibor Schuster, Francine M Ducharme, Brenda MacGibbon, Tracie A Barnett
BACKGROUND: Current evidence regarding the relationship between childhood obesity, decreased response to inhaled corticosteroids (ICS), and poor asthma control is conflicting. OBJECTIVES: We assessed if obesity: i) is associated with time-to-first exacerbation among children with asthma initiating Step-3 maintenance therapies; ii) modifies the effectiveness of Step-3 therapies. METHODS: A retrospective cohort study was conducted from clinical data linked to health and drug administrative databases...
January 27, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29372000/highly-active-antiretroviral-therapy-alters-sperm-parameters-and-testicular-antioxidant-status-in-diet-induced-obese-rats
#8
Ibukun P Oyeyipo, Bongekile T Skosana, Frans P Everson, Hans Strijdom, Stefan S du Plessis
The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the in vivo effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART...
January 2018: Toxicological Research
https://www.readbyqxmd.com/read/29369602/evaluation-of-the-amoxicillin-concentrations-in-amniotic-fluid-placenta-umbilical-cord-blood-and-maternal-serum-two-hours-after-oral-administration
#9
(no author information available yet)
OBJECTIVES: Amoxicillin is a broad-spectrum beta-lactam antibiotic. Due to its low toxicity, it is commonly used in obstetrics. The objective of this study was to assess amoxicillin concentrations in amniotic fluid, umbilical blood, placenta and maternal serum two hours following oral administration among pregnant women at term and to assess obstetric and non-obstetric factors that might affect amoxicillin's penetration of these tissues. MATERIALS AND METHODS: A total of 30 full-term pregnant women who qualified for elective Caesarean delivery were included in the study...
December 25, 2017: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/29367871/rapid-clearance-of-erythrodermic-psoriasis-with-apremilast
#10
Evangelia Papadavid, Georgios Kokkalis, Georgios Polyderas, Konstantinos Theodoropoulos, Dimitrios Rigopoulos
Background: Apremilast is a new immunomodulatory drug, a small molecule inhibitor of PDE4, which down-regulates the expression of multiple pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin 17, interleukin 23. Main observations: We describe a case of a 54-year-old man with erythroderma in the course of psoriasis (PASI=49), with contraindications to other psoriasis therapies, in whom total clearance of skin lesions was achieved by day 20 after therapy with apremilast at a dose of 30 mg bid (ΔPASI = 100)...
December 1, 2017: Journal of Dermatological Case Reports
https://www.readbyqxmd.com/read/29357416/improved-protocols-for-the-study-of-urinary-electrolyte-excretion-and-blood-pressure-in-rodents-use-of-gel-food-and-stepwise-changes-in-diet-composition
#11
Jonathan M Nizar, Nadine Bouby, Lise Bankir, Vivek Bhalla
Many experimental protocols in rodents require the comparison of groups that are fed different diets. Changes in dietary electrolyte and/or fat content can influence food intake, which can potentially introduce bias or confound the results. Unpalatable diets slow growth or cause weight loss, which is exacerbated by housing the animals in individual metabolic cages or by surgery. For balance studies in mice, small body weight and food intake, and low urinary flow can amplify these challenges. Powder food can be administered as a gel with the addition of a desired amount of water, electrolytes, drugs (if any), and a small amount of agar...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29357102/methods-of-estimating-kidney-function-for-drug-dosing-in-special-populations
#12
REVIEW
Laura A Hart, Gail D Anderson
International guidelines recommend the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method to monitor kidney function in chronic kidney disease using either creatinine- or cystatin C-based estimation methods. The choice of an estimation method to determine dosage for renally eliminated drugs is not as clear. For the majority of currently marketed drugs, the Cockcroft-Gault equation with the Jaffe method, a non-isotope dilution mass spectrometry, standardized serum creatinine, was used to estimate kidney function to recommend dosing adjustment in kidney impairment...
January 22, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29350758/obesity-and-pediatric-drug-development
#13
Janelle D Vaughns, Laurie S Conklin, Ying Long, Panli Zheng, Fahim Faruque, Dionna J Green, John N van den Anker, Gilbert J Burckart
There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies...
January 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29330781/a-review-of-the-methods-and-associated-mathematical-models-used-in-the-measurement-of-fat-free-mass
#14
REVIEW
Jaydeep Sinha, Stephen B Duffull, Hesham S Al-Sallami
Fat-free mass (FFM) represents the lean component of the body devoid of fat. It has been shown to be a useful predictor of drug dose requirements, particularly in obesity where the excess fat mass does not contribute to drug clearance. However, measuring FFM involves complex and/or expensive experimental methodologies that preclude their use in routine clinical practice. Thus, models to predict FFM from readily measurable variables, such as body weight and height, have been developed and are used in both population pharmacokinetic modelling and clinical practice...
January 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29328026/clinical-efficacy-of-s-adenosylmethionine-in-patients-with-non-alcoholic-steatohepatitis-and-chronic-kidney-disease-i-ii-stage
#15
A Antoniv, N Antofiychuk, T Danylyshina, I Trefanenko, V Shuper
The article presents a theoretical generalization of the results of the clinical efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis (NASH) in comorbidity with obesity and chronic kidney disease (CKD) of the 1st-2nd stages. The objective of the article was to determine the likely effect of S-adenosylmethionine and Meldonium on the clinical course of non-alcoholic steatohepatitis (NASH) and chronic kidney disease (CKD) of the I-II stages. We examined 75 patients with NASH with comorbid obesity I degree and CKD I and II dgrees...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29327229/leopoldia-comosa-prevents-metabolic-disorders-in-rats-with-high-fat-diet-induced-obesity
#16
T Casacchia, F Scavello, C Rocca, M C Granieri, G Beretta, D Amelio, F Gelmini, A Spena, R Mazza, C C Toma, Tommaso Angelone, Giancarlo Statti, T Pasqua
PURPOSE: Obesity is the main feature of a complex illness known as metabolic syndrome. Anti-obesogenic therapies are often associated with side effects and represent a high cost in conventional pharmacological approaches. New strategies based on natural remedies are under continuous investigation. Leopoldia comosa (L.) Parl. (L. comosa) is a spontaneous plant with diuretic, anti-inflammatory and antioxidant properties. Recently, a hypoglycemic activity mediated by inhibition of carbohydrate digestion has been identified...
January 11, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29304216/hypertension-control-in-adults-with-ckd-in-china-baseline-results-from-the-chinese-cohort-study-of-chronic-kidney-disease-c-stride
#17
Zhe Yan, Yu Wang, Shaomei Li, Jinwei Wang, Luxia Zhang, Huibin Tan, Sumin Li, Lin Yang, Huaying Pei, Liping Zhang, Yan Wang, Jianzhao Duan, Sumin Jiao, Minghui Zhao, Shuxia Fu
Background: Hypertension contributes to increased morbidity and mortality in the chronic kidney disease (CKD) population. Studies on blood pressure control in CKD patients in China are limited. In this study, we aimed to describe the status of blood pressure control in Chinese CKD patients based on the first national prospective CKD cohort data. Methods: A subgroup of Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) participants with hypertension at baseline was included in the present study...
January 3, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29297106/idalopirdine-a-selective-5-ht6-receptor-antagonist-reduces-food-intake-and-body-weight-in-a-model-of-excessive-eating
#18
Magdalena Kotańska, Klaudia Lustyk, Adam Bucki, Monika Marcinkowska, Joanna Śniecikowska, Marcin Kołaczkowski
Obesity, from early childhood onwards, is a common societal problem. The overconsumption of sweet, salty and high-fat products are the main factors that cause excessive weight gain. It is therefore necessary to search for new drugs that affect satiety centers and reduce the sense of hunger and caloric intake. It has been suggested that the blockade of 5-HT6 receptors may reduce food intake, and since idalopirdine is a clinically tested, selective 5HT6 receptor antagonist, it was chosen to be examined in animal models of obesity...
January 3, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29291393/patchouli-alcohol-protects-against-ischemia-reperfusion-induced-brain-injury-via-inhibiting-neuroinflammation-in-normal-and-obese-mice
#19
Li-Li Wei, Yong Chen, Qiong-Yang Yu, Yuhui Wang, George Liu
Almost all of the candidate drugs for ischemic stroke failed to be translated from bench to beside. One important reason is that animals used in experimental studies cannot mimic ischemic patients due to lack of comorbidities like hypertension, diabetes and obesity. Therefore, it is better to test candidate drugs not only in normal animals but also in animals with comorbidities. Patchouli alcohol (PA), a natural tricyclic sesquiterpene in the traditional Chinese herb Pogostemonisherba, is well recognized for its anti-inflammation function in various inflammatory diseases...
December 29, 2017: Brain Research
https://www.readbyqxmd.com/read/29279243/antiobesity-and-emetic-effects-of-a-short-length-peptide-yy-analog-and-its-pegylated-and-alkylated-derivatives
#20
Ayumu Niida, Yoko Kanematsu-Yamaki, Tomoko Asakawa, Yoshimasa Ishimura, Hisashi Fujita, Kouta Matsumiya, Naoki Nishizawa, Yusuke Adachi, Taisuke Mochida, Kazue Tsuchimori, Mariko Yoneyama-Hirozane, Junichi Sakamoto, Hideki Hirabayashi, Hideo Fukui, Shiro Takekawa, Taiji Asami
Neuropeptide Y2 receptor (Y2R) agonism is an important anorectic signal and a target of antiobesity drug discovery. Recently, we synthesized a short-length Y2R agonist, PYY-1119 (4-imidazolecarbonyl-[d-Hyp24,Iva25,Pya(4)26,Cha27,36,γMeLeu28,Lys30,Aib31]PYY(23-36), 1) as an antiobesity drug candidate. Compound 1 induced marked body weight loss in diet-induced obese (DIO) mice; however, 1 also induced severe vomiting in dogs at a lower dose than the minimum effective dose administered to DIO mice. The rapid absorption of 1 after subcutaneous administration caused the severe vomiting...
December 8, 2017: Bioorganic & Medicinal Chemistry
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