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https://www.readbyqxmd.com/read/28934782/the-dose-dependent-effects-of-ketoprofen-on-dynamic-pain-after-open-heart-surgery
#1
Vedat Eljezi, Claire Biboulet, Henri Boby, Pierre Schoeffler, Bruno Pereira, Christian Duale
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce postoperative pain, in both static (i.e., at rest) and dynamic contexts (e.g., during coughing or mobilization), and reduced doses could improve their efficacy/tolerance balance. OBJECTIVES: To test this hypothesis of efficacy after open heart surgery, in which NSAIDs are poorly used, particularly for safety concerns. STUDY DESIGN: Randomized, double-blind trial. SETTING: Single-center, French university hospital...
September 2017: Pain Physician
https://www.readbyqxmd.com/read/28933266/intravenous-paracetamol-dosing-guidelines-for-pain-management-in-pre-term-neonates-using-the-paediatric-study-decision-tree
#2
P Mian, C A J Knibbe, E A M Calvier, D Tibboel, K Allegaert
BACKGROUND: Intravenous paracetamol (acetaminophen) has not been licensed for analgesia in preterm neonates or infants < 2 years, respectively, in Europe and the United States. A variety of dosing regimens is therefore used off-label. Because evidence supports the use of the same target mean steady state paracetamol concentration (Cssmean, 9-11 mg/L) for pain relief in neonates compared to older children and adults, dosing regimens based on this Cssmean were evaluated in a two-step approach...
September 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28932176/effect-of-udp-glucuronosyltransferase-ugt-1a-polymorphism-rs8330-and-rs10929303-on-glucuronidation-status-of-acetaminophen
#3
Huma Mehboob, Imtiaz Mahmood Tahir, Tahira Iqbal, Sadaf Saleem, Sofia Perveen, Aboubakker Farooqi
Interindividual variability in polymorphic uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) ascribed to genetic diversity is associated with relative glucuronidation level among individuals. The present research was aimed to study the effect of 2 important single nucleotide polymorphisms (SNPs; rs8330 and rs10929303) of UGT1A1 gene on glucuronidation status of acetaminophen in healthy volunteers (n = 109). Among enrolled volunteers, 54.13% were male (n = 59) and 45.87% were female (n = 50). The in vivo activity of UGT1A1 was investigated by high-performance liquid chromatography-based analysis of glucuronidation status (ie, acetaminophen and acetaminophen glucuronide) in human volunteers after oral intake of a single dose (1000 mg) of acetaminophen...
July 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28919358/perfused-human-hepatocyte-microtissues-identify-reactive-metabolite-forming-and-mitochondria-perturbing-hepatotoxins
#4
Cliff Rowe, Mohsen Shaeri, Emma Large, Terri Cornforth, Angela Robinson, Tomasz Kostrzewski, Rowena Sison-Young, Christopher Goldring, Kevin Park, David Hughes
Hepatotoxins cause liver damage via many mechanisms but the formation of reactive metabolites and/or damage to liver mitochondria are commonly implicated. We assess 3D human primary hepatocyte microtissues as a platform for hepatotoxicity studies with reactive metabolite-forming and mitochondria-perturbing compounds. We show that microtissues formed from cryopreserved human hepatocytes had bile canaliculi, transcribed mRNA from genes associated with xenobiotic metabolism and expressed functional cytochrome P450 enzymes...
September 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28894628/tigernut-cyperus-esculentus-l-milk-as-a-potent-nutri-drink-for-the-prevention-of-acetaminophen-induced-hepatotoxicity-in-a-murine-model
#5
Nnenna Ola Onuoha, Nneoma Oleh Ogbusua, Augustine N Okorie, Chukwunonso E C C Ejike
AIM/BACKGROUND: Given the prevalence of toxicants in foods, beauty products, etc., and the increasing demand for "green" products, there is a need for the development of "nutri-drinks" with hepatoprotective properties. The usefulness of tigernut milk (TNM) in preventing acetaminophen (APAP)-induced liver injury was, therefore, investigated. MATERIALS AND METHODS: A total of 25 rats were randomized into five equal groups. Four groups were treated with 0, 500, 1000, and 2000 kg/mg body weight (bw) TNM, respectively, per os for 2 weeks before they were challenged with 2500 mg/kg bw APAP...
July 2017: Journal of Intercultural Ethnopharmacology
https://www.readbyqxmd.com/read/28893642/enzyme-inducing-effects-of-berberine-on-cytochrome-p450-1a2-in-vitro-and-in-vivo
#6
Bo Jiang, Liyuan Meng, Feng Zhang, Xiaoling Jin, Guiliang Zhang
AIMS: Berberine (BER) is an important anti-bacterial drug from Chinese herbal medicine and a novel drug candidate for preclinical development in recent years. Here we provide evidence that the effects of berberine on cytochrome P450 (CYP) 1A2 in vitro and in vivo. MAIN METHODS: Real-time polymerase chain reaction and western blotting analysis were employed to evaluate the CYP1A2 mRNA levels and protein expression. The enzyme activity was assessed by the metabolic rate of phenacetin to acetaminophen by LC-MS/MS method...
September 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28891786/a-framework-and-case-studies-for-evaluation-of-enzyme-ontogeny-in-children-s-health-risk-evaluation
#7
Gary Ginsberg, Suryanarayana V Vulimiri, Yu-Sheng Lin, Jayaram Kancherla, Brenda Foos, Babasaheb Sonawane
Knowledge of the ontogeny of Phase I and Phase II metabolizing enzymes may be used to inform children's vulnerability based upon likely differences in internal dose from xenobiotic exposure. This might provide a qualitative assessment of toxicokinetic (TK) variability and uncertainty pertinent to early lifestages and help scope a more quantitative physiologically based toxicokinetic (PBTK) assessment. Although much is known regarding the ontogeny of metabolizing systems, this is not commonly utilized in scoping and problem formulation stage of human health risk evaluation...
September 11, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28887752/comparison-of-antipyretic-efficacy-of-intravenous-iv-acetaminophen-versus-oral-po-acetaminophen-in-the-management-of-fever-in-children
#8
Shuvendu Roy, A K Simalti
OBJECTIVE: To assess the dynamics of the onset of antipyretic efficacy of intravenous (IV) acetaminophen vs. oral (PO) acetaminophen in the management of fever in children. METHODS: This observational single-dose study was conducted at Department of Pedriatrics, Army Hospital (Research and Referral), a multispecialty tertiary care center in New Delhi in fever patients to assess the antipyretic efficacy of IV acetaminophen 15 mg/kg/dose vs. PO acetaminophen 15 mg/kg/dose over 6 h...
September 9, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28873028/randomized-prospective-evaluation-of-intraoperative-intravenous-acetaminophen-in-pediatric-adenotonsillectomy
#9
Christopher A Roberts, Shivani Shah-Becker, Ashley O'Connell Ferster, Aaron Baker, Lauren E Stahl, Khaled Sedeek, Michele M Carr
Objective To establish the safety and efficacy of single-dose intraoperative intravenous (IV) acetaminophen in postoperative pain management following adenotonsillectomy in addition to a standardized regimen of oral pain medication. Study Design Randomized, controlled prospective clinical trial. Setting Single academic medical center. Subjects and Methods Patients between the ages of 3 and 17 years scheduled for tonsillectomy or adenotonsillectomy by a single surgeon between December 2014 and November 2016 were recruited...
September 1, 2017: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/28872689/metabolic-interactions-between-acetaminophen-paracetamol-and-two-flavonoids-luteolin-and-quercetin-through-in-vitro-inhibition-studies
#10
Lei Cao, Awewura Kwara, David J Greenblatt
OBJECTIVES: Excessive exposure to acetaminophen (APAP, paracetamol) can cause liver injury through formation of a reactive metabolite that depletes hepatic glutathione and causes hepatocellular oxidative stress and damage. Generation of this metabolite is mediated by Cytochrome-P450 (CYP) isoforms, mainly CYP2E1. A number of naturally occurring flavonoids can mitigate APAP-induced hepatotoxicity in experimental animal models. Our objective was to determine the mechanism of these protective effects and to evaluate possible human applicability...
September 5, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28867745/non-toxic-level-of-acetaminophen-potentiates-carbon-tetrachloride-induced-hepatotoxicity-in-mice
#11
Shiori Fukaya, Hiroki Yoshioka, Tadahiro Okano, Akito Nagatsu, Nobuhiko Miura, Tsunemasa Nonogaki, Satomi Onosaka
A wide range of medications are routinely used to maintain and improve human health. Hence, it is essential that we understand and predict adverse effects caused by the combined use of multiple medications. In the present study, we investigated whether the combination of carbon tetrachloride (CCl4) and acetaminophen (APAP) had a detrimental effect on the liver. Mice injected with APAP (100 mg/kg) showed no significant changes in hepatic injury markers (alanine aminotransferase and aspartate aminotransferase), histopathological findings, pro-inflammatory cytokine levels, or hepatic oxidative stress...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28867424/psychosocial-and-behavioral-factors-in-acetaminophen-related-acute-liver-failure-and-liver-injury
#12
Carla Pezzia, Corron Sanders, Suzanne Welch, Angela Bowling, William M Lee
OBJECTIVES: Acetaminophen overdoses result in nearly 500 deaths annually and a much larger number of hospitalizations. Suicidal overdoses are exceeded in number in the United States by unintentional overdoses. We evaluated clinical, demographic and psychosocial factors among unintentional and intentional overdose patients whose acetaminophen (APAP) toxicity had resulted in acute liver failure. We hypothesized that APAP overdose patients would be more likely to suffer from behavioral health issues and display higher impulsivity scores than the general population...
October 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28867200/application-of-x-ray-sensors-for-in-line-and-non-invasive-monitoring-of-mass-flow-rate-in-continuous-tablet-manufacturing
#13
Sudarshan Ganesh, Rachel Troscinski, Nicholas Schmall, Jongmook Lim, Zoltan Nagy, Gintaras Reklaitis
The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in continuous manufacturing. The sensor independently measures x-ray attenuation and cross-correlation velocimetry of particulate flow in real-time. Steady-state flow rates of blends comprised primarily of acetaminophen and microcrystalline-cellulose are monitored using the sensor, with simultaneous weighing scale measurements, in order to calibrate the sensor and investigate the measurement accuracy...
August 31, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28835871/multimodal-pain-management-in-older-elective-arthroplasty-patients
#14
Elaine Brooks, Susan H Freter, Susan K Bowles, David Amirault
BACKGROUND: Pain management after elective arthroplasty in older adults is complicated due to the risk of undertreatment of postoperative pain and potential adverse effects from analgesics, notably opioids. Using combinations of analgesics has been proposed as potentially beneficial to achieve pain control with lower opioid doses. OBJECTIVE: We compared a multimodal pain protocol with a traditional one, in older elective arthroplasty patients, measuring self-rated pain, incidence of postoperative delirium, quantity and cost of opioid analgesics consumed...
September 2017: Geriatric Orthopaedic Surgery & Rehabilitation
https://www.readbyqxmd.com/read/28829522/opioid-pain-medication-prescriptions-obtained-through-emergency-medical-visits-in-the-veterans-health-administration
#15
Michael A Grasso, Zachary D W Dezman, Clare T Grasso, David A Jerrard
OBJECTIVE: This study sought to characterize national patterns for opioid pain medication (OPM) prescriptions received during emergency medical encounters in the Veterans Health Administration (VA). DESIGN: The authors conducted a retrospective study of all emergency department (ED) visits by adults in the VA between January 2009 and June 2015. We examined demographics, comorbidities, utilization measures, diagnoses, and prescriptions. MAIN OUTCOME MEASURES: The percentage of ED visits that culminated in the receipt of a prescription for an OPM...
March 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28827191/silver-nanoparticles-protect-acetaminophen-induced-acute-hepatotoxicity-a-biochemical-and-histopathological-approach
#16
Mohd Salim Reshi, Chhavi Uthra, Deepa Yadav, Samta Sharma, Asha Singh, Anjali Sharma, Amita Jaswal, Neelu Sinha, Sadhana Shrivastava, Sangeeta Shukla
The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 μg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals...
August 19, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28827156/induction-of-mitochondrial-biogenesis-protects-against-acetaminophen-hepatotoxicity
#17
Kuo Du, Anup Ramachandran, Mitchell R McGill, Abdellah Mansouri, Tarik Asselah, Anwar Farhood, Benjamin L Woolbright, Wen-Xing Ding, Hartmut Jaeschke
Mitochondrial biogenesis (MB) is an adaptive response to maintain metabolic homeostasis after mitochondrial dysfunction. Induction of MB during APAP hepatotoxicity has not been studied. To investigate this, mice were treated with toxic doses of APAP and euthanized between 0 and 96 h. At early time points, APAP caused both mitochondrial dysfunction and reduction of mitochondrial mass, indicated by reduced activity of electron transport chain (ETC) complexes I and IV and depletion of mitochondrial DNA (mtDNA), respectively...
October 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28816033/selection-of-12-hour-sustained-release-acetaminophen-paracetamol-formulation-through-comparison-of-pharmacokinetic-profiles-of-4-sustained-release-prototype-formulations-and-standard-acetaminophen-formulation-an-open-label-randomized-proof-of-principle-pharmacokinetic
#18
Yong Yue, Dongzhou J Liu
Acetaminophen (APAP; paracetamol), a widely used analgesic and antipyretic, is available in modified-release and immediate-release (IR) formulations requiring 3- or 4-times-daily dosing. This phase 1 open-label crossover study compared pharmacokinetic profiles of single 2000-mg doses of 4 different sustained-release (SR) formulations of APAP (designed to allow twice-daily dosing) against two 1000-mg doses (taken 6 hours apart) of standard IR APAP in 14 healthy volunteers. The primary end point was duration of time that plasma APAP concentration exceeded a plasma concentration (TC ) of 4 μg/mL...
August 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28816026/evaluation-of-a-12-hour-sustained-release-acetaminophen-paracetamol-formulation-a-randomized-3-way-crossover-pharmacokinetic-and-safety-study-in-healthy-volunteers
#19
Yong Yue, Agron Collaku, Dongzhou J Liu
Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (TC≥4μg/mL )...
August 16, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28815997/bioequivalence-and-safety-of-twice-daily-sustained-release-paracetamol-acetaminophen-compared-with-3-and-4-times-daily-paracetamol-a-repeat-dose-crossover-pharmacokinetic-study-in-healthy-volunteers
#20
Dongzhou J Liu, Agron Collaku
Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily)...
August 16, 2017: Clinical Pharmacology in Drug Development
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