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Jeffrey J Cies, Wayne S Moore, Adela Enache, Arun Chopra
OBJECTIVE: This study aims to describe the population pharmacokinetics and pharmacodynamic target attainment of meropenem in critically ill children. METHODS: The study involved a retrospective medical record review from a 189-bed, freestanding children's tertiary care teaching hospital of patients ages 1 to 9 years who received meropenem with concurrent therapeutic drug monitoring. RESULTS: There were 9 patients ages 1 to 9 years (mean age, 3...
July 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Richard L Rauck, D Alexander Oh, Neil Singla, Christian Koch, Neha Parikh, Srinivas Nalamachu, Daniel Wilson, Jin Yu, Santosh Vetticaden
OBJECTIVE: Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. METHODS: Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0...
September 23, 2017: Current Medical Research and Opinion
Rakesh Awasthi, Guohua An, Maureen D Donovan, Laura L Boles Ponto
The medical use of marijuana is increasing, yet little is known about the exposure-response relationship for its psychoactive effects. It is well known that the plasma concentrations of the principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), do not directly correlate to the observed psychoactive effects. The purpose of this research was to use an effect-compartment modeling approach to predict and relate the concentrations of the psychoactive components (THC and its active metabolite) in the "hypothetical" effect-site compartment to the observed psychoactive effects...
September 20, 2017: Journal of Pharmaceutical Sciences
Sahl Khalid Bedri, Katharina Fink, Ali Manouchehrinia, Wangko Lundström, Ingrid Kockum, Tomas Olsson, Jan Hillert, Anna Glaser
Genetic variants within some cytokine receptor genes have been associated with MS susceptibility, including IL7RA and IL2RA. As these genes are expressed by cells targeted by immune-modulatory drugs, we explored the potential role of their gene products as biomarkers in monitoring MS treatment. We assessed the impact of natalizumab followed by fingolimod on the intra-individual changes of plasma protein levels of sIL-7Rα, sIL-2Rα and also sIL-6R and sgp130 in MS patients. During natalizumab treatment we observed a decline in sgp130 and sIL-7Rα levels, while subsequent fingolimod treatment lead to increased sgp130 and sIL-7Rα and decreased sIL-2Rα levels...
September 20, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Jan Bures, Anna Jirkovska, Vit Sestak, Hana Jansova, Galina Karabanovich, Jaroslav Roh, Martin Sterba, Tomas Simunek, Petra Kovarikova
Novel dexrazoxane derivative JR-311 was prepared to investigate structure-activity relationships and mechanism(s) of protection against anthracycline cardiotoxicity. Its cardioprotective, antiproliferative, iron (Fe) chelation and inhibitory and/or depletory activities on topoisomerase IIbeta (TOP2B) were examined and compared with dexrazoxane. While in standard assay, JR-311 failed in both cardioprotection and depletion of TOP2B, its repeated administration to cell culture media led to depletion of TOP2B and significant protection of isolated rat neonatal ventricular cardiomyocytes from daunorubicin-induced damage...
September 20, 2017: Toxicology
Athena F Zuppa, Martha A Q Curley
Sedation is a mainstay of therapy for critically ill children. Although necessary in the care of the critically ill child, sedative drugs are associated with adverse effects, such as disruption of circadian rhythm, altered sleep, delirium, potential neurotoxicity, and immunosuppression. Optimal approaches to the sedation of the critically ill child should include identification of sedation targets and sedation interruptions, allowing for a more individualized approach to sedation. Further research is needed to better understand the relationship between critical illness and sedation pharmacokinetics and pharmacodynamics, the impact of sedation on immune function, and the genetic implications on drug disposition and response...
October 2017: Pediatric Clinics of North America
Roy M Fleischmann, Frank Wagner, Alan J Kivitz, Heikki T Mansikka, Nasser Khan, Ahmed A Othman, Amit Khatri, Feng Hong, Ping Jiang, Melanie Ruzek, Robert J Padley
OBJECTIVE: Tumor necrosis factor (TNF) and interleukin (IL)-17 independently contribute to the pathophysiology of rheumatoid arthritis (RA). ABT-122 is a novel dual variable domain immunoglobulin that selectively and simultaneously targets human TNF and IL-17A in an effort to evoke a greater clinical response than targeting either cytokine alone. This communication reports the pooled safety, tolerability, and exploratory pharmacodynamics of ABT-122 from two phase 1, placebo-controlled, multiple-dose studies in patients with primarily inactive RA...
September 21, 2017: Arthritis & Rheumatology
Xin Zhang, Eric Chen Quin Lam, Mary E Seger, David Coutant, Laiyi Chua, Lai Hock Tan, Danny Soon, Helle Linnebjerg
LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products with identical amino acid sequences. This was a phase 1 single-site, randomized, subject- and investigator-blinded, 4-treatment, 4-period crossover study to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of LY IGlar and IGlar at 2 different doses. Fasted healthy subjects were randomly assigned to receive 2 single doses of LY IGlar and IGlar (0.3 and 0.6 U/kg for each product). Blood samples were collected up to 24 hours postdose to assess PK, and a euglycemic clamp lasting up to 24 hours postdose was conducted to assess PD...
September 21, 2017: Clinical Pharmacology in Drug Development
Seung-Hee Ki, Jin-Ho Rhim, Jae-Hong Park, Young-Jin Han, Yong-Pil Cho, Tae-Won Kwon, Byung-Moon Choi, Gyu-Jeong Noh
AIM: Regional cerebral oxygen saturation (rSO2 ) is currently the most used measure in clinical practice to monitor cerebral ischemia in patients undergoing carotid endarterectomy (CEA). Although end-tidal carbon dioxide (PET CO2 ) is known as a factor that influences rSO2 , the relationship between PET CO2 and rSO2 has not been quantitatively evaluated in patients with severe arteriosclerosis. This study aimed to evaluate the effect of PET CO2 on rSO2 in patients undergoing CEA under general anaesthesia...
September 23, 2017: British Journal of Clinical Pharmacology
Emma D Deeks
GP2015 is the second biosimilar of the reference p75 TNF receptor-Fc fusion protein etanercept. It is approved for use in all indications for which reference etanercept is approved, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis and paediatric plaque psoriasis. GP2015 has similar physiochemical and pharmacodynamic properties to those of reference etanercept, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers...
September 23, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Torben Biester, Olga Kordonouri, Thomas Danne
PURPOSE OF REVIEW: Faster aspart is a new formulation of insulin aspart (IAsp) produced by adding the excipients niacinamide and L-arginine. As this new, "ultra-rapid insulin" is available in the EU-market and Canada, the pharmacokinetic and pharmacodynamics data is summarized. RECENT FINDINGS: Faster aspart shows an earlier onset of appearance of insulin in the bloodstream after subcutaneous administration and an earlier onset of glucose-lowering action and a higher glycemic effect within the first 30 min...
September 23, 2017: Current Diabetes Reports
Susanne Alt, Axel Helmstädter
Depending on the timing of market entry, radical innovations can be distinguished from incremental innovations. Whereas a radical innovation typically is the first available derivative of a drug class, incremental innovations are launched later and show a certain benefit compared with the radical innovation. Here, we use historical market data relating to pharmacokinetic (PK), pharmacodynamic (PD), and other drug-related properties to investigate which derivatives within certain drug classes have been most successful on the market...
September 20, 2017: Drug Discovery Today
Sara Cascone, Gaetano Lamberti, Ornella Piazza, Roberto Andrea Abbiati, Davide Manca
Remifentanil based anesthesia is nowadays spread worldwide. This drug is characterized by a rapid onset of the analgesic effects, but also a rapid onset of the side effects. For this reason, the knowledge of the remifentanil concentration in the human body is a key topic in anesthesiology. The aims of this work are to propose and validate a physiologically based pharmacokinetic model capable to predict both the pharmacokinetics and pharmacodynamics of remifentanil, and to take into account the inter-individual differences among the patients (such as the height and body mass)...
September 19, 2017: European Journal of Pharmaceutical Sciences
Bo Zhang, Ting Jiang, Yanyan Tuo, Kai Jin, Zimiao Luo, Wei Shi, Heng Mei, Yu Hu, Zhiqing Pang, Xinguo Jiang
Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy...
September 19, 2017: Cancer Letters
Payam Dehghani, Andrea Lavoie, Shahar Lavi, Jennifer J Crawford, Sebastian Harenberg, Rodney H Zimmermann, Jeff Booker, Sheila Kelly, Warren J Cantor, Shamir R Mehta, Akshay Bagai, Shaun G Goodman, Asim N Cheema
OBJECTIVES: Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI. METHODS AND RESULTS: Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily...
October 2017: American Heart Journal
Jia-Li Hu, Jun Yang, Yin-Bin Zhou, Ping Li, Ran Han, Dian-Chun Fang
Background\Aim: Quadruple daily administration of proton-pump inhibitor (PPI) therapy achieves potent acid inhibition, and combined with amoxicillin, with its pharmacodynamic and pharmacokinetic characteristics, may be efficient for Helicobacter pylori eradication. We compared the efficacy of two optimized high-dose dual therapies with a bismuth-containing quadruple regimen for treating H. pylori infection. Rabeprazole dosages for H. pylori eradication were also evaluated. PATIENTS AND METHODS: Treatment-naive and H...
September 2017: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
Juan He, Enqiang Mao, Feng Jing, Huiting Jiang, Wenyun Xu, Wanhua Yang, Erzhen Chen
OBJECTIVE: To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD) of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD. METHODS: The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled...
September 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Yan-Jun Zhang, Li-Li Liu, Yun Wu, Jun-Hua Hu, Xiu-Juan Chang, Wei Xiao, En-Xiang Chao
To evaluate the rationality of alcohol precipitation technology of Biqiu granule by investigating its effect on serum histamine, IgE, IL-4, IFN and TNF-α. The contents of cafferic acid and rosmarinic acid were used as the evaluation indexes, and some factors affecting index were firstly evaluated by Plackett-Burman design; then alcohol precipitation technology was further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. The best alcohol precipitation conditions were as follows: the relative density of herb liquor was 1...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Xue-E Yu, Jian-Ping Qin, Jia-Chun Li, Wen-Zhe Huang, Zhen-Zhong Wang, Wei Xiao
To analyze and identify the chemical constituents from Yinyanghuo Zonghuangtong capsule by using UPLC/Q-TOF-MS/MS. Chromatographic separation was carried out on an Agilent SB-C₁₈ column (2.1 mm×100 mm, 1.8 μm) at the temperature of 30 ℃. The mobile phase was 0.1% formic acid and acetonitrile by gradient elution, with a flow rate at 0.30 mL•min⁻¹, and the injection volume of 2 μL. The MS spectrum was acquired in both negative and positive ion modes using ESI ion source. Based on relative accurate molecular weight, secondary mass spectrometry pyrolysis fragments and chromatographic peak retention time, as well as fragmentation regularity summarized from reference substance and the literature, we could effectively identify the chemical structure of the components under test...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Xian-Rong Lai, Bang-Hua Zhou, Ming-Sheng Du, Hai-Jie Zheng, Zhi-Peng Geng, Jia-Chuan Li, Xian-Li Meng, Yi Zhang, Jing Zhang
To establish a method for determining the contents of six alkaloids (jatrorrhizine hydrochloride, columbamine hydrochloride, epiberberine hydrochloride, coptisine hydrochloride, palmatine hydrochloride, berberine hydrochloride) in six types of Coptidis Rhizoma pieces (crude pieces, ginger juice stir-fried pieces, vinegar stir-fried pieces, wine steamed pieces, wine stir-fried pieces, evodiae juice stir-fried pieces) by RP-HPLC, and explore the relationship with the curative effect of traditional Chinese medicine (TCM) and pharmacodynamics results...
December 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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