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Clinical pharmacokinetics

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https://www.readbyqxmd.com/read/28528396/penetration-of-vancomycin-into-the-cerebrospinal-fluid-a-systematic-review
#1
REVIEW
Jessica E Beach, Jerrold Perrott, Ricky D Turgeon, Mary H H Ensom
INTRODUCTION: Infectious disease and pharmacokinetic textbooks indicate that vancomycin has poor penetration into the central nervous system due to its hydrophilic nature and high molecular weight. Recent literature suggests that penetration of vancomycin into cerebrospinal fluid (CSF) is higher than previously reported; therefore, we conducted a systematic review to assess the penetration of vancomycin into CSF. METHODS: We searched the MEDLINE, EMBASE, and CENTRAL electronic databases for English-language human studies evaluating serum and CSF concentrations of intravenous vancomycin...
May 20, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28528229/sensitive-uhplc-ms-ms-quantitation-and-pharmacokinetic-comparisons-of-multiple-alkaloids-from-fuzi-beimu-and-single-herb-aqueous-extracts-following-oral-delivery-in-rats
#2
Yanyan Xu, Yamei Li, Pengjie Zhang, Bin Yang, Huanyu Wu, Xuejun Guo, Yubo Li, Yanjun Zhang
Aconiti Lateralis Radix Praeparata- Fritillariae Thunbergii bulbus, namely Fuzi- Beimu in Chinese, is a classic herb pair whose combined administration was prohibited according to the rule of "Eighteen antagonisms". However, incompatibility of Fuzi and Beimu has become controversial because of the application supported by many recorded ancient prescriptions and increasing modern researches and clinical practice. The present study aimed to investigate the pharmacokinetic differences of multiple alkaloids from Fuzi- Beimu and the single herb aqueous extracts following oral delivery in rats...
May 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28528008/-role-of-therapeutic-drug-monitoring-in-pulmonary-infections
#3
REVIEW
C Padoin
Pulmonary infections are common and caused by a wide range of viruses, bacteria, parasites and fungi. They consist of lower respiratory tract infections with community and hospital acquired acute pneumonia, bronchitis, lung abscess, fungal infections and tuberculosis. The management of these infections should be based on guidelines that take into account the microorganisms most frequently involved as a basis for empirical treatment, with identification of causative microorganisms allowing targeted treatments...
May 17, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28527782/protective-roles-of-bioactive-peptides-during-ischemia-reperfusion-injury-from-bench-to-bedside
#4
REVIEW
Dongdong Wu, Jun Wang, Honggang Wang, Ailing Ji, Yanzhang Li
Ischemia-reperfusion (I/R) is a well-known pathological condition which may lead to disability and mortality. I/R injury remains an unresolved and complicated situation in a number of clinical conditions, such as cardiac arrest with successful reanimation, as well as ischemic events in brain and heart. Peptides have many attractive advantages which make them suitable candidate drugs in treating I/R injury, such as low toxicity and immunogenicity, good solubility property, distinct tissue distribution pattern, and favorable pharmacokinetic profile...
May 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28527735/advances-in-combination-therapy-of-lung-cancer-rationales-delivery-technologies-and-dosage-regimens
#5
REVIEW
Lan Wu, Donglei Leng, Dongmei Cun, Camilla Foged, Mingshi Yang
Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i...
May 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28527510/saposhnikoviae-divaricata-a-phytochemical-pharmacological-and-pharmacokinetic-review
#6
REVIEW
Jenny Kreiner, Edwin Pang, George Binh Lenon, Angela Wei Hong Yang
Saposhnikoviae divaricata (Turcz.) Schischk (SD) is a traditional Chinese herb commonly used to treat clinical conditions such as rheumatism and allergic rhinitis. This review article evaluates a collection of works on in vitro and biochemical studies of SD. The discourse on the diverse class of chromones and coumarins in SD offers an insight to the pharmacological effects of these bioactive constituents as anti-inflammatory, analgesic, immunoregulatory, antioxidative, and anti-proliferative agents. It is highlighted that there is a structural relationship between the constituents and bioactive activities, which in effect provides a valid reasoning and reaffirm the use of SD in the treatment of the pathologies in Chinese medicine...
April 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28527133/a-phase-ii-study-of-antibody-drug-conjugate-tak-264-mln0264-in-previously-treated-patients-with-advanced-or-metastatic-pancreatic-adenocarcinoma-expressing-guanylyl-cyclase-c
#7
Khaldoun Almhanna, David Wright, Teresa Macarulla Mercade, Jean-Luc Van Laethem, Antonio Cubillo Gracian, Carmen Guillen-Ponce, Jason Faris, Carolina Muriel Lopez, Richard A Hubner, Johanna Bendell, Alain Bols, Jaime Feliu, Naureen Starling, Peter Enzinger, Devalingham Mahalingham, Wells Messersmith, Huyuan Yang, Adedigbo Fasanmade, Hadi Danaee, Thea Kalebic
Background This phase II open-label, multicenter study evaluated the efficacy, safety, and tolerability of TAK-264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC). Methods Patients with advanced or metastatic pancreatic adenocarcinoma expressing GCC (H-score ≥ 10) received TAK-264 1.8 mg/kg on day 1 of a 21-day cycle as a 30-min intravenous infusion for up to 1 year or until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR [complete response + partial response (PR)])...
May 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28527109/erratum-to-clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#8
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
May 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28526963/incorporation-of-the-time-varying-postprandial-increase-in-splanchnic-blood-flow-into-a-pbpk-model-to-predict-the-effect-of-food-on-the-pharmacokinetics-of-orally-administered-high-extraction-drugs
#9
Rachel H Rose, David B Turner, Sibylle Neuhoff, Masoud Jamei
Following a meal, a transient increase in splanchnic blood flow occurs that can result in increased exposure to orally administered high-extraction drugs. Typically, physiologically based pharmacokinetic (PBPK) models have incorporated this increase in blood flow as a time-invariant fed/fasted ratio, but this approach is unable to explain the extent of increased drug exposure. A model for the time-varying increase in splanchnic blood flow following a moderate- to high-calorie meal (TV-Q Splanch) was developed to describe the observed data for healthy individuals...
May 19, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28526486/plasma-concentrations-of-transdermal-fentanyl-and-buprenorphine-in-pigs-sus-scrofa-domesticus
#10
Suzanne Osorio Lujan, Walid Habre, Youssef Daali, Zhaoxin Pan, Peter W Kronen
OBJECTIVE: To determine the absorption characteristics of fentanyl and buprenorphine administered transdermally in swine. STUDY DESIGN: A randomized comparative experimental trial. ANIMALS: Twenty-four Yorkshire gilts weighing 27.8±2.2 kg (mean±standard deviation). METHODS: Animals were randomly assigned to different doses of transdermal patches (TPs) of fentanyl (50 μg hour(-1), 75 μg hour(-1) and 100 μg hour(-1)) or buprenorphine (35 μg hour(-1) and 70 μg hour(-1)), once or twice...
January 11, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28526158/revisiting-oxycodone-analgesia-a-review-and-hypothesis
#11
REVIEW
Xiulu Ruan, Ken F Mancuso, Alan D Kaye
Oxycodone, a semisynthetic opioid analgesic, is widely used in clinical practice. Oxycodone and morphine seem to be equally effective and equipotent; however, morphine is 10 times more potent than oxycodone when given epidurally. This article provides an updated review of the basic pharmacology of oxycodone with a special focus on pharmacokinetic/pharmacodynamics properties. The controversy regarding oxycodone-mediated effects for visceral pain via agonism and the possible role of peripheral opioid analgesia are discussed in the present investigation in an attempt to propose a plausible explanation to the perplexing question of oxycodone analgesia...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28526056/the-blood-schizonticidal-activity-of-tafenoquine-makes-an-essential-contribution-to-its-prophylactic-efficacy-in-nonimmune-subjects-at-the-intended-dose-200%C3%A2-mg
#12
REVIEW
Geoffrey Dow, Bryan Smith
Tafenoquine (TQ) is an 8-aminoquinoline anti-malarial being developed for malaria prophylaxis. It has been generally assumed that TQ, administered prophylactically, acts primarily on the developing exoerythrocytic stages of malaria parasites (causal prophylaxis), and that polymorphisms in metabolic enzymes thought to impact the activity of other 8-aminoquinolines also inhibit this property of TQ. Furthermore, it has been suggested that a diagnostic test for CYP2D6 metabolizer status might be required. In field studies in which metabolic status was not an exclusion criteria, TQ has been shown to exhibit similar prophylactic efficacy as blood schizonticidal drugs (mefloquine)...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28524709/pharmacokinetics-of-ingenol-mebutate-gel-under-maximum-use-conditions-in-large-treatment-areas
#13
Alicia D Bucko, Michael Jarratt, Dowling B Stough, Laerke Kyhl, John Villumsen, Anders Hall
PURPOSE: Actinic keratoses (AKs) exist on a continuum with squamous cell carcinoma and can occur as sub-clinical and clinically visible lesions in cancerized fields on sun-damaged skin. Ingenol mebutate effectively treats AKs on areas up to 25 cm(2), but actinic keratosis can affect larger areas of skin. This trial evaluated systemic exposure and safety of ingenol mebutate gel on larger areas of skin under maximum use conditions. METHODS: Phase I, multicenter, open-label, uncontrolled, non-randomized trial...
May 19, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28524459/prognostic-role-of-conventional-and-dynamic-contrast-enhanced-mri-in-optic-pathway-gliomas
#14
Nutchawan Jittapiromsak, Ping Hou, Ho-Ling Liu, Jia Sun, John M Slopis, T Linda Chi
BACKGROUND AND PURPOSE: The natural history of optic pathway glioma (OPG) is highly variable and unpredictable. We present a pilot study of the prognostic role of conventional and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) in the evaluation of OPG. METHODS: We retrospectively reviewed 17 patients with 20 pretreatment OPG lesions who underwent conventional and DCE MRI between January 2010 and December 2016. Conventional MRI was evaluated for enhancement pattern, cystic component, optic nerve tortuosity, optic nerve dural ectasia, and optic nerve perineural thickening...
May 19, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28524005/rivaroxaban-metabolism-pharmacologic-properties-and-drug-interactions
#15
Tomas Kvasnicka, Ivana Malikova, Zuzana Zenahlikova, Karolína Kettnerova, Radka Brzezkova, Tomas Zima, Jan Ulrych, Jan Briza, Ivan Netuka, Jan Kvasnicka
BACKGROUND: Rivaroxaban represents a selective direct inhibitor of activated coagulation factor X (FXa) having peroral bioavailability and prompt onset of action. OBJECTIVE: The absorbtion of rivaroxaban is quick, reaching maximum plasma concentration 2-4 hours following its administration. Peroral bioavailability is high (80-100 %) and pharmacokinetic variability is considered to be moderate (coefficient of variation 30-40 %). This review discusses the properties, drug interactions, pharmacokinetics and clinical indications of rivaroxaban...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28523450/a-review-of-the-clinical-pharmacokinetics-pharmacodynamics-and-immunogenicity-of-vedolizumab
#16
REVIEW
Maria Rosario, Nathanael L Dirks, Catherine Milch, Asit Parikh, Michael Bargfrede, Tim Wyant, Eric Fedyk, Irving Fox
Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations...
May 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28523172/roles-of-roflumilast-a-selective-phosphodiesterase-4-inhibitor-in-airway-diseases
#17
REVIEW
Theerasuk Kawamatawong
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases. Both diseases have incompletely distinct pathophysiology, clinical manifestation, and treatment responsiveness. Pulmonary and systemic inflammations are the hallmarks of COPD. Most asthma responds to inhaled corticosteroid (ICS) treatment. In contrast, COPD is a corticosteroid-resistant disease. Bronchodilators are a preferred treatment method of COPD, with the aim of improving symptoms and preventing exacerbation...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28523106/discovery-of-fluorine-containing-benzoxazinyl-oxazolidinones-for-the-treatment-of-multidrug-resistant-tuberculosis
#18
Hongyi Zhao, Yu Lu, Li Sheng, Zishuo Yuan, Bin Wang, Weiping Wang, Yan Li, Chen Ma, Xiaoliang Wang, Dongfeng Zhang, Haihong Huang
A novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. Compound 21 exhibited not only outstanding in vitro activity with a MIC value of 0.25-0.50 μg/mL against drug-susceptible H37Rv strain and two clinically isolated drug-resistant Mycobacterium tuberculosis strains, but also acceptable in vitro ADME/T properties. Moreover, this compound displayed excellent mouse pharmacokinetic profiles with an oral bioavailability of 102% and a longer elimination half-life of 4...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28523103/toward-resolving-the-resveratrol-conundrum-synthesis-and-in-vivo-pharmacokinetic-evaluation-of-bcp-resveratrol
#19
Yi Ling Goh, Yan Ting Cui, Vishal Pendharkar, Vikrant A Adsool
Over the last few decades, resveratrol has gained significance due to its impressive array of biological activities; however, its true potential as a drug has been severely constrained by its poor bioavailability. Indeed, several studies have implicated this bioavailability trait as a major road-block to resveratrol's potential clinical applications. To mitigate this pharmacokinetic issue, we envisioned a tactical bioisosteric modification of resveratrol to bicyclo[1.1.1]pentane (BCP) resveratrol. Relying on the beneficial bioisosteric potential demonstrated by the BCP-scaffold, we hypothesized that BCP-resveratrol would have an inherently better in vivo PK profile as compared to its natural counterpart...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522195/a-dpp-iv-resistant-glucagon-like-peptide-2-dimer-with-enhanced-activity-against-radiation-induced-intestinal-injury
#20
Jintao Gu, Shuo Liu, Nan Mu, Tonglie Huang, Wangqian Zhang, Huadong Zhao, Zhen Shu, Cun Zhang, Qiang Hao, Weina Li, Xiaochang Xue, Wei Zhang, Yingqi Zhang
Although radiotherapy is a highly effective treatment for abdominal or pelvic cancer patients, it can increase the incidence of severe gastrointestinal (GI) toxicity. As an intestinal growth factor, glucagon-like peptide 2 (GLP-2) has been shown to improve the preclinical models of both short bowel syndrome and inflammatory bowel disease by stimulating intestinal growth. Teduglutide ([Gly(2)]GLP-2), a recombinant human GLP-2 variant, has a prolonged half-life and stability as compared to the native GLP-2 peptide, but still requires daily application in the clinic...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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