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pharmacokinetics, brain, plasma

Le-Le Yang, Na Xiao, Xiao-Wei Li, Yong Fan, Raphael N Alolga, Xiao-Yue Sun, Shi-Lei Wang, Ping Li, Lian-Wen Qi
Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G...
October 24, 2016: Scientific Reports
Marcos Guilherme da Cunha, Gilson César Nobre Franco, Marcelo Franchin, John A Beutler, Severino Matias de Alencar, Masaharu Ikegaki, Pedro Luiz Rosalen
In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array...
October 20, 2016: Toxicology Letters
Kinga Sałat, Adrian Podkowa, Natalia Malikowska, Felix Kern, Jörg Pabel, Ewelina Wojcieszak, Katarzyna Kulig, Klaus T Wanner, Beata Strach, Elżbieta Wyska
BACKGROUND AND PURPOSE: Since GABAergic dysfunction underlies a variety of neurological and psychiatric disorders, numerous strategies leading to the augmentation of GABAergic neurotransmission have been introduced. One of them is the inhibition of GABA reuptake from the synaptic cleft mediated by four plasma membrane GABA transporters (GAT1-4). GAT1 which is exclusively expressed in the brain is an interesting target for centrally acting drugs. In this research, pharmacological properties of a novel, highly potent and selective inhibitor of GAT1, the guvacine derivative named DDPM-2571, were assessed in vivo...
October 19, 2016: Neuropharmacology
Shehla Akbar, Fazal Subhan, Nasiara Karim, Muhammad Shahid, Nisar Ahmad, Gowhar Ali, Wajahat Mahmood, Khwaja Fawad
BACKGROUND: Diabetic neuropathy is the most prevalent, persistent and debilitating complication of diabetes mellitus often coupled with vulvodynia that may present as an isolated symptom or as a part of constellation of other neuropathic abnormalities. OBJECTIVE: Flavonoids have selective affinity for GABA receptors and 6-methoxyflavanone (6-MeOF) is a positive allosteric modulator of GABA responses at human recombinant GABAA receptors. GABAergic and opioidergic system inhibition have been shown to facilitate neuropathic pain...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Peter R Bieck, Mark Leibowitz, D Richard Lachno, Edouard Ledent, Robert Padich, Stan Jhee
To assess the primary metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a sensitive biomarker for norepinephrine transporter (NET) function and the relationship of DHPG measured peripherally and centrally, NET was antagonized with 80 mg/d atomoxetine for 18 days. Twelve healthy subjects were treated with atomoxetine in an open-label, multiple-dose exploratory study. Plasma atomoxetine reached steady state by day 6, and the pharmacokinetic results demonstrated availability of atomoxetine to the central nervous system...
October 15, 2016: Journal of Clinical Psychopharmacology
Kayoko Kanamitsu, Ryosuke Arakawa, Yuichi Sugiyama, Tetsuya Suhara, Hiroyuki Kusuhara
The effect of drugs in the central nervous system (CNS) is closely related to occupancy of their target receptor. In this study, we integrated plasma concentrations, in vitro/in vivo data for receptor or protein binding, and in silico data, using a physiologically based pharmacokinetic model, to examine the predictability of receptor occupancy in humans. The occupancy of the dopamine D2 receptor and the plasma concentrations of the antipsychotic drugs quetiapine and perospirone in humans were collected from the literature or produced experimentally...
July 30, 2016: Drug Metabolism and Pharmacokinetics
Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Marc Pretze, Prama Pallavi, Mareike Roscher, Sarah Klotz, Julio Caballero, Uta Binzen, Wolfgang Greffrath, Rolf-Detlef Treede, Martin C Harmsen, Mathias Hafner, Benito Yard, Carmen Wängler, Björn Wängler
To mitigate pre-transplantation injury in organs of potential donors N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in brain dead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [(18)F]F-NOD [(18)F]5 for in vivo assessment of NOD's elimination kinetics by means of PET imaging. [(18)F]5 was synthesized with reproducible high radiochemical yield and purity (>98%) as well as high specific activities (>20 GBq/µmol)...
October 12, 2016: Journal of Medicinal Chemistry
Xiao-Yu Xiao, Ying-Xian Zhu, Ju-Yuan Bu, Guo-Wei Li, Jian-Hui Zhou, Shao-Peng Zhou
The purpose of the present study was to evaluate the neuroprotective efficacy of optimized thymoquinone loaded PLGA-chitosan nanoparticles delivered via nose to brain route in the rodent cerebral ischemia-reperfusion model. The neuroprotective efficacy of the optimized thymoquinone loaded PLGA-chitosan nanoparticles was evaluated in middle cerebral artery occluded rats by various pharmacodynamic and biochemical studies. The pharmacokinetics of thymoquinone loaded PLGA-chitosan nanoparticles in the brain and blood plasma together with qualitative localization of florescent labelled PLGA-chitosan nanoparticles in brain tissues were also determined...
2016: BioMed Research International
Martin Valis, Jiri Masopust, Oldrich Vysata, Jakub Hort, Rafael Dolezal, Jiri Tomek, Jan Misik, Kamil Kuca, Jana Zdarova Karasova
Although some studies have described the pharmacokinetics and pharmacodynamics of donepezil in the peripheral compartment, studies focused on drug transport across the blood-brain barrier are still very rare. To our knowledge, the fluctuation in the cerebrospinal fluid concentration of donepezil after administration of the drug has not been described in the literature so far. We recruited 16 patients regularly taking a standard therapeutic dose of donepezil (10 mg per day). All patients (Caucasian race) were treated for at least three months with a stable dose of 10 mg per day prior to sample collection...
October 7, 2016: Neurotoxicity Research
S Michael Owens, Gerald T Pollard, James L Howard, Timothy R Fennell, Rodney W Snyder, F Ivy Carroll
JDTic is a potent and selective κ-opioid receptor (KOR) antagonist that reverses U50,488-induced diuresis in rats. It partitions into brain with a duration of action lasting for weeks. In a search for KOR antagonists that do not accumulate in the brain, we compared single doses of five methylated JDTic analogs (RTI-97, -194, -212, -240, and -241) for reversal of U50,488 diuresis and pharmacokinetic (PK) properties. All six compounds showed potent and selective KOR antagonism in a [(35)S]GTPγS binding assay...
October 4, 2016: ACS Chemical Neuroscience
Sandra Ventura, Márcio Rodrigues, Sarah Pousinho, Amílcar Falcão, Gilberto Alves
A simple and rapid high-performance liquid chromatography method with diode-array detection (HPLC-DAD) using microextraction by packed sorbent (MEPS) during the sample preparation step was developed and validated to quantify lamotrigine (LTG) in rat plasma and brain samples. MEPS variables such as pH, number of draw-eject cycles, and washing and desorption conditions were optimized. The chromatographic resolution of LTG and chloramphenicol, used as internal standard (IS), was accomplished in less than 5min on a C18 column, at 35°C, using an isocratic elution with acetonitrile (13%), methanol (13%) and water-triethylamine (99...
November 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Rita Citraro, Emilio Russo, Antonio Leo, Roberto Russo, Carmen Avagliano, Michele Navarra, Antonio Calignano, Giovambattista De Sarro
We evaluated the effects of ACEA (selective cannabinoid (CB)1 receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB1 and CB2 receptor agonist) and N-palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy. PEA, ACEA or WIN intraperitoneal (i.p.) administration decreased the severity of tonic-clonic seizures. We also studied the effects of PEA, WIN or ACEA after co-administration with NIDA-41020 (CB1 receptor antagonist) or GW6471 (PPAR-α antagonist) and compared the effects of WIN, ACEA and PEA in order to clarify their mechanisms of action...
September 20, 2016: European Journal of Pharmacology
Dustin Wooten, Nicolas J Guehl, Eline E Verwer, Timothy M Shoup, Daniel L Yokell, Nevena Zubcevik, Neil Vasdev, Ross D Zafonte, Keith A Johnson, Georges El Fakhri, Marc David Normandin
: [(18)F]T807 is a PET radiotracer developed for imaging tau protein aggregates, which are implicated in neurological disorders including Alzheimer's disease (AD) and traumatic brain injury (TBI). The current study characterizes [(18)F]T807 pharmacokinetics in human subjects using dynamic PET imaging and metabolite-corrected arterial input functions. METHODS: Nine subjects (4 control, 3 with history of TBI, 2 mild cognitive impairment (MCI) due to suspected AD) underwent dynamic PET imaging for up to 120 minutes after bolus injection of [(18)F]T807 with arterial blood sampling...
September 22, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Joshua Elmore, Ora Dillon-Carter, John Partilla, Kayla N Ellefsen, Marta Concheiro, Masaki Suzuki, Kenner C Rice, Marilyn A Huestis, Michael H Baumann
3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance and the β-keto analog of 3,4-methylenedioxy-N-methylamphetamine (MDMA). It is well established that MDMA metabolism produces bioactive metabolites. Here we tested the hypothesis that methylone metabolism in rats can form bioactive metabolites. First, we examined the pharmacokinetics (PK) of methylone and its metabolites after subcutaneous (sc) methylone administration (3, 6, 12 mg/kg) to male rats fitted with intravenous (iv) catheters for repeated blood sampling...
September 23, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
S Vajapeyam, C Stamoulis, K Ricci, M Kieran, T Young Poussaint
BACKGROUND AND PURPOSE: Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. MATERIALS AND METHODS: Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software...
September 15, 2016: AJNR. American Journal of Neuroradiology
Julius O Enoru, Barbara Yang, Sesha Krishnamachari, Ernesto Villanueva, William DeMaio, Adiba Watanyar, Ramesh Chinnasamy, Jeffrey B Arterburn, Ruth G Perez
Parkinson's disease (PD) is a neurodegenerative aging disorder in which postmortem PD brain exhibits neuroinflammation, as well as synucleinopathy-associated protein phosphatase 2A (PP2A) enzymatic activity loss. Based on our translational research, we began evaluating the PD-repurposing-potential of an anti-inflammatory, neuroprotective, and PP2A stimulatory oral drug that is FDA-approved for multiple sclerosis, FTY720 (fingolimod, Gilenya®). We also designed two new FTY720 analogues, FTY720-C2 and FTY720-Mitoxy, with modifications that affect drug potency and mitochondrial localization, respectively...
2016: PloS One
Inas A Abdallah, Peng Huang, Jing Liu, David Y Lee, Lee-Yuan Liu-Chen, Hazem E Hassan
Levo-tetrahydropalmatine (l-THP) is an alkaloid isolated from Chinese medicinal herbs of the Corydalis and Stephania genera. It has been used in China for more than 40 years mainly as an analgesic with sedative/hypnotic effects. Despite its extensive use, its metabolism has not been quantitatively studied, nor there a sensitive reliable bioanalytical method for its quantification simultaneously with its metabolites. As such, the objective of this study was to develop and validate a sensitive and selective HPLC method for simultaneous quantification of l-THP and its desmethyl metabolites l-corydalmine (l-CD) and l-corypalmine (l-CP) in rat plasma and brain tissues...
September 8, 2016: Biomedical Chromatography: BMC
Erik Melander, Camilla Eriksson, Britt Jansson, Ulf Göransson, Margareta Hammarlund-Udenaes
This study provides a new method for quantifying the cyclotide kalata B1 in both plasma and brain homogenate. Cyclotides are ultra-stable peptides with three disulfide bonds that are interesting from a drug development perspective as they can be used as scaffolds. In this study we describe a new validated LC-MS/MS method with high sensitivity and specificity for kalata B1. The limit of quantification was 2 ng/mL in plasma and 5 ng/gmL in brain homogenate. The method was linear in the range 2 - 10 000 ng/mL for plasma and 5 - 2000 ng/g for brain...
September 7, 2016: Biopolymers
Reema Narayan, Mohan Singh, OmPrakash Ranjan, Yogendra Nayak, Sanjay Garg, Gopal V Shavi, Usha Y Nayak
The present paper is aimed at development of functionalized risperidone liposomes for brain targeting through nasal route for effective therapeutic management of schizophrenia. The risperidone liposomes were prepared by thin film hydration method. Various parameters such as lipid ratio and lipid to drug ratio were optimized by using Design-Expert(®) Software to obtain high entrapment with minimum vesicle size. The surface of the optimized liposomes was modified by coating stearylamine and MPEG-DSPE for enhanced penetration to the brain...
October 15, 2016: Life Sciences
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