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https://www.readbyqxmd.com/read/29667370/systems-toxicology-approach-to-identifying-paracetamol-overdose
#1
Chantelle L Mason, Joseph Leedale, Sotiris Tasoulis, Ian Jarman, Daniel J Antoine, Steven D Webb
Paracetamol (acetaminophen (APAP)) is one of the most commonly used analgesics in the United Kingdom and the United States. However, exceeding the maximum recommended dose can cause serious liver injury and even death. Promising APAP toxicity biomarkers are thought to add value to those used currently and clarification of the functional relationships between these biomarkers and liver injury would aid clinical implementation of an improved APAP toxicity identification framework. The framework currently used to define an APAP overdose is highly dependent upon time since ingestion and initial dose; information that is often highly unpredictable...
April 18, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29662027/pharmacokinetic-pharmacodynamic-model-for-the-testosterone-suppressive-effect-of-leuprolide-in-normal-and-prostate-cancer-rats
#2
Dong-Seok Lee, Sook-Jin Kim, Go-Wun Choi, Yong-Bok Lee, Hea-Young Cho
This study developed the pharmacokinetic (PK)-pharmacodynamic (PD) model of the testosterone-suppressive effect of leuprolide for evaluation of the sustained release (SR) depot and leuprolide solution in rats with or without prostate cancer. Six groups of rats were divided by the routes of administration (intravenous and subcutaneous injection) and kinds of formulation (vehicle, leuprolide solution, and SR depot). The PK profile after subcutaneous injection of leuprolide solution could be well-described by the one-compartment model...
April 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29661413/pharmacokinetic-and-pharmacodynamic-study-of-intranasal-and-intravenous-dexmedetomidine
#3
A Li, V M Yuen, S Goulay-Dufaÿ, Y Sheng, J F Standing, P C L Kwok, M K M Leung, A S Leung, I C K Wong, M G Irwin
BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM ). METHODS: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 μg kg-1 dexmedetomidine, either i...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29661412/pharmacokinetic-pharmacodynamic-model-for-propofol-for-broad-application-in-anaesthesia-and-sedation
#4
D J Eleveld, P Colin, A R Absalom, M M R F Struys
BACKGROUND: Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a central or effect-site compartment. Our aim was to develop a PK-PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications. METHODS: Propofol PK data were obtained from 30 previously published studies, five of which also contained BIS observations...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29659885/results-from-the-survey-of-antibiotic-resistance-soar-2014-16-in-ukraine-and-the-slovak-republic
#5
D Torumkuney, T Pertseva, E Bratus, A Dziublik, V Yachnyk, A Liskova, O Sopko, K Malynovska, I Morrissey
Objectives: To determine antibiotic susceptibility in isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from Ukraine and the Slovak Republic. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: S. pneumoniae isolates collected in Ukraine (n = 100) showed susceptibility rates ≥97% for amoxicillin, amoxicillin/clavulanic acid, penicillin [intravenous (iv) non-meningitis] and fluoroquinolones, between 83% and 86% for oral penicillin, macrolides and cefaclor, and 75% for trimethoprim/sulfamethoxazole...
April 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29659884/results-from-the-survey-of-antibiotic-resistance-soar-2014-16-in-greece
#6
D Torumkuney, J Papaparaskevas, I Morrissey
Objectives: To determine antimicrobial susceptibility in isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from patients with community-acquired respiratory tract infections in Greece. Methods: MICs were determined by CLSI broth microdilution and susceptibility assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: A total of 99 S. pneumoniae and 52 H. influenzae isolates were collected...
April 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29659883/results-from-the-survey-of-antibiotic-resistance-soar-2014-16-in-the-czech-republic
#7
D Torumkuney, H Zemlickova, M Maruscak, I Morrissey
Objectives: To determine the antibiotic susceptibility of isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from patients with community-acquired respiratory infections in the Czech Republic. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: S. pneumoniae isolates (n = 200) showed high rates of susceptibility (>95%) to amoxicillin, amoxicillin/clavulanic acid, penicillin [intravenous (iv) non-meningitis], ceftriaxone, cefuroxime and the fluoroquinolones using CLSI breakpoints...
April 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29659882/results-from-the-survey-of-antibiotic-resistance-soar-2014-16-in-bulgaria-romania-serbia-and-croatia
#8
D Torumkuney, M Nica, I Nistor, R Vatcheva-Dobrevska, V Petrovic, A Stoica, B Hanicar, Dj Antic, I Morrissey
Objectives: To determine antibiotic susceptibility of isolates of Streptococcus pneumoniae (n = 573) and Haemophilus influenzae (n = 345) collected in 2014-16 from Bulgaria, Romania, Serbia and Croatia. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: Among S. pneumoniae, susceptibility was generally lowest in Romania and Serbia and highest in Bulgaria...
April 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29659881/results-from-the-survey-of-antibiotic-resistance-soar-2014-16-in-russia
#9
D Torumkuney, N Mayanskiy, M Edelstein, S Sidorenko, R Kozhevin, I Morrissey
Objectives: To determine antibiotic susceptibility in isolates of Streptococcus pneumoniae and Haemophilus influenzae collected in 2014-16 from Russia. Methods: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results: A total of 279 S. pneumoniae and 279 H. influenzae were collected. Overall, 67.0% of S. pneumoniae were penicillin susceptible by CLSI oral/EUCAST and 93...
April 1, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29651591/importance-of-qt-rr-hysteresis-correction-in-studies-of-drug-induced-qtc-interval-changes
#10
Marek Malik, Christine Garnett, Katerina Hnatkova, Lars Johannesen, Jose Vicente, Norman Stockbridge
QT/RR hysteresis and QT/RR adaptation are interlinked but separate physiological processes signifying how quickly and how much QT interval changes when heart rate changes, respectively. While QT interval duration is, as a rule, corrected for heart rate in terms of the QT/RR adaptation, the correction for QT/RR hysteresis is frequently omitted in studies of drug-induced QTc changes. This study used data from previously conducted thorough QT studies to investigate the extent of QTc errors caused by omitting the correction for QT/RR hysteresis, particularly in small clinical investigations...
April 12, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29649858/pharmacokinetics-of-enrofloxacin-hcl-2h-2-o-enro-c-in-dogs-and-pk-pd-monte-carlo-simulations-against-leptospira-sp
#11
Hector Sumano, Luis Ocampo, Graciela Tapia, C de Jesus Mendoza, Lilia Gutierrez
Pharmacokinetics/pharmacodynamics (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2H2 O (Enro-C), as well as Monte Carlo simulations based on composite MIC50 and MIC90 vs. Leptospira sp., were carried out in dogs after their IM and oral administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by means of high performance liquid chromatography (HPLC). Maximum plasma concentration values after oral administration were 1.47 ± 0.19 µg/mL and 5.3 ± 0.84 µg/mL for Enro-R and Enro-C, respectively, and 1...
April 12, 2018: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29649606/pk-pd-characterization-of-combined-antimicrobial-agents-a-real-challenge-and-an-urgent-need
#12
EDITORIAL
William Couet
No abstract text is available yet for this article.
April 9, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29623729/pharmacokinetic-considerations-for-pediatric-patients-receiving-analgesia-in-the-intensive-care-unit-targeting-postoperative-ecmo-and-hypothermia-patients
#13
G A Zeilmaker, P Pokorna, P Mian, E D Wildschut, C A J Knibbe, E H J Krekels, K Allegaert, D Tibboel
Adequate postoperative analgesia in pediatric patients in the intensive care unit (ICU) matters, since untreated pain is associated with negative outcomes. Compared to routine postoperative patients, children undergoing hypothermia (HT) or extracorporeal membrane oxygenation (ECMO), or recovering after cardiac surgery likely display non-maturational differences in pharmacokinetics (PK) and pharmacodynamics (PD). These differences warrant additional dosing recommendations to optimize pain treatment. Areas covered: Specific populations within the ICU will be discussed with respect to expected variations in PK and PD for various analgesics...
April 6, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29619607/pharmacokinetic-pharmacodynamic-considerations-of-beta-lactam-antibiotics-in-adult-critically-ill-patients
#14
REVIEW
Anne M Masich, Mojdeh S Heavner, Jeffrey P Gonzales, Kimberly C Claeys
PURPOSE OF REVIEW: Beta-lactam antibiotics are commonly prescribed in critically ill patients for a variety of infectious conditions. Our understanding of how critical illness alters beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) is rapidly evolving. RECENT FINDINGS: There is a growing body of literature in adult patients demonstrating that physiological alterations occurring in critically ill patients may limit our ability to optimally dose beta-lactam antibiotics to reach these PK/PD targets...
April 4, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29618565/pharmacokinetics-of-rifapentine-and-rifampin-in-a-rabbit-model-of-tuberculosis-and-correlation-with-clinical-trial-data
#15
Dalin Rifat, Brendan Prideaux, Radojka M Savic, Michael E Urbanowski, Teresa L Parsons, Brian Luna, Mark A Marzinke, Alvaro A Ordonez, Vincent P DeMarco, Sanjay K Jain, Veronique Dartois, William R Bishai, Kelly E Dooley
In clinical trials of two rifamycin antibiotics (rifampin and rifapentine) for treating tuberculosis (TB), patients with cavitary lung lesions did not appear to derive benefit from rifapentine. Rifapentine was found not to outperform rifampin, despite a lower minimum inhibitory concentration against Mycobacterium tuberculosis in mouse models of TB. To understand these findings, we have developed a rabbit model of TB that reliably develops lung cavities with features similar to those of patients with pulmonary cavitary TB...
April 4, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29610208/avibactam-pharmacokinetic-pharmacodynamic-targets
#16
Wright W Nichols, Paul Newell, Ian Critchley, Todd Riccobene, Shampa Das
Avibactam is a novel non-β-lactam β-lactamase inhibitor that has been approved in the USA and Europe for use in combination with ceftazidime. Combinations of avibactam with aztreonam or ceftaroline fosamil have also been clinically evaluated. Until recently, there has been very little precedence of which pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitudes are appropriate to use for β-lactamase inhibitors in population PK modeling for analyzing potential doses and susceptibility breakpoints. For avibactam, several preclinical studies using different in vitro and in vivo models have been conducted to identify the PK/PD index of avibactam and the magnitude of exposure necessary for effect in combination with ceftazidime, aztreonam, or ceftaroline fosamil...
April 2, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29604374/insulin-delivery-systems-combined-with-microneedle-technology
#17
Xuan Jin, Dan Dan Zhu, Bo Zhi Chen, Mohammad Ashfaq, Xin Dong Guo
Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs...
March 28, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29593380/bioequivalence-of-a-biosimilar-enoxaparin-sodium-to-clexane-%C3%A2-after-single-100-mg-subcutaneous-dose-results-of-a-randomized-double-blind-crossover-study-in-healthy-volunteers
#18
Javier Martínez González, Mayte Monreal, Ignacio Ayani Almagia, Jordi Llaudó Garín, Lourdes Ochoa Díaz de Monasterioguren, Ibón Gutierro Adúriz
Purpose: To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence of a biosimilar enoxaparin to the reference drug, and to assess its safety and tolerability in healthy volunteers. Patients and methods: A randomized, double-blind, crossover, 2-sequence, single-dose study was conducted in healthy volunteers of both sexes. Participants were sequentially and randomly administered single subcutaneous injections of enoxaparin 100 mg manufactured by Rovi (test; Madrid, Spain) and Clexane® (enoxaparin 100 mg manufactured by Sanofi, reference) separated by a 1-week washout period...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29584861/linezolid-pharmacokinetics-in-mdr-tb-a-systematic-review-meta-analysis-and-monte-carlo-simulation
#19
James Millard, Henry Pertinez, Laura Bonnett, Eva Maria Hodel, Véronique Dartois, John L Johnson, Maxine Caws, Simon Tiberi, Mathieu Bolhuis, Jan-Willem C Alffenaar, Geraint Davies, Derek J Sloan
Objectives: The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods: We defined linezolid PK/PD targets for efficacy (fAUC0-24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0-24 and fCmin for published doses...
March 23, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29582860/covariate-determinants-of-effective-dosing-regimens-for-time-dependent-beta-lactam-antibiotics-for-critically-ill-patients
#20
Milan Kaska, Eduard Havel, Iva Selke-Krulichova, Petr Safranek, Jan Bezouska, Jirina Martinkova
AIMS: Critically ill patients undergoing aggressive fluid resuscitation and treated empirically with hydrosoluble time-dependent beta-lactam antibiotics are at risk for sub-therapeutic plasma concentrations. The aim of this study was to assess the impact of two covariates - creatinine clearance (Clcr ) and cumulative fluid balance (CFB) on pharmacokinetics/pharmacodynamics (PK/PD) target attainment within a week of treatment with meropenem (ME) or piperacillin/tazobactam (PIP/TZB). METHODS: In this prospective observational pharmacokinetic (PK) study, 18 critically ill patients admitted to a surgical Intensive Care Unit (ICU) were enrolled...
March 27, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
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