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pharmacokinetics, brain, plasma

Ailing Hui, Huayang Yin, Zheng Zhang, An Zhou, Jingchao Chen, Li Yang, Zeyu Wu, Wencheng Zhang
Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study...
March 9, 2018: Drug Delivery and Translational Research
Joshua I Hardt, Joel S Perlmutter, Christopher J Smith, Kevin L Quick, Ling Wei, Subhasish K Chakraborty, Laura L Dugan
BACKGROUND AND OBJECTIVES: Fullerene-based compounds are a novel class of molecules being developed for a variety of biomedical applications, with nearly 1000 publications in this area in the last 4 years alone. One such compound, the e,e,e-methanofullerene(60)-63-tris malonic acid (designated C3 ), is a potent catalytic superoxide dismutase mimetic which has shown neuroprotective efficacy in a number of animal models of neurologic disease, including Parkinsonian Macaca fascicularis monkeys...
March 8, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Eman A Alraddadi, Ryan Lillico, Jonathan L Vennerstrom, Ted M Lakowski, Donald W Miller
Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little is known about its pharmacokinetic profile. Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption. Rats were dosed orally with low dose (10 mg/kg) or high dose (70 mg/kg)13 C-labeled CM. Blood samples were removed at various time points. Muscle and brain tissue were collected at the conclusion of the study...
March 8, 2018: Pharmaceutics
Hua-Shan Liu, Shih-Wei Chiang, Hsiao-Wen Chung, Ping-Huei Tsai, Fei-Ting Hsu, Nai-Yu Cho, Chao-Ying Wang, Ming-Chung Chou, Cheng-Yu Chen
BACKGROUND AND OBJECTIVE: To investigate the feasibility of histogram analysis of the T2*-based permeability parameter volume transfer constant (Ktrans ) for glioma grading and to explore the diagnostic performance of the histogram analysis of Ktrans and blood plasma volume (vp ). METHODS: We recruited 31 and 11 patients with high- and low-grade gliomas, respectively. The histogram parameters of Ktrans and vp , derived from the first-pass pharmacokinetic modeling based on the T2* dynamic susceptibility-weighted contrast-enhanced perfusion-weighted magnetic resonance imaging (T2* DSC-PW-MRI) from the entire tumor volume, were evaluated for differentiating glioma grades...
March 2018: Computer Methods and Programs in Biomedicine
Hisanao Izumi, Yasuharu Shinoda, Takashi Saito, Takaomi Saido, Keita Sato, Yasushi Yabuki, Yotaro Matsumoto, Yoshitomi Kanemitsu, Yoshihisa Tomioka, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga
Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of elderly dementia in the world. At present, acetylcholine inhibitors, such as donepezil, galantamine and rivastigmine, are used for AD therapy, but the therapeutic efficacy is limited. We recently proposed T-type voltage gated Ca2+ channels (T-VGCCs) enhancer as a new therapeutic candidate for AD. In the current study, we confirmed the pharmacokinetics of SAK3 in the plasma and brain of mice using ultra performance liquid chromatography-tandem mass spectrometry...
March 3, 2018: Neuroscience
Maja Johansson, Maria Månsson, Lars-Eric Lins, Bruce Scharschmidt, Magnus Doverskog, Torbjörn Bäckström
RATIONALE: GR3027 is a novel small molecule GABA-A receptor-modulating steroid antagonist, which in non-clinical studies has shown promise for treatment of human disorders due to allosteric over-activation of GABA-A receptors by neurosteroids, such as allopregnanolone. We here studied its safety, pharmacokinetics, and ability to inhibit allopregnanolone effects in humans. METHODS: Safety and pharmacokinetics were studied in healthy adult males receiving ascending single or multiple oral GR3027 vs...
February 28, 2018: Psychopharmacology
Benedicte Lelievre, Marie Briet, Charlotte Godon, Pierre Legras, Jeremie Riou, Patrick Vandeputte, Bertrand Diquet, Jean Philippe Bouchara
Cerebral Scedosporium infections usually occur in lung transplant recipients as well as in immunocompetent patients in the context of near-drowning. Voriconazole is the first-line treatment. The diffusion of voriconazole through the blood-brain barriers in the context of cerebral infection and cyclosporine administration is crucial and remains a matter of debate. To address this issue, the pharmacokinetics of voriconazole were assessed in the plasma, cerebrospinal fluid (CSF), and brain, in an experimental model of cerebral scedosporiosis in rats receiving or not cyclosporine...
February 28, 2018: Journal of Pharmacology and Experimental Therapeutics
Gaurav Kumar, Pankaj Paliwal, Sumedha Mukherjee, Nishant Patnaik, Sairam Krishnamurthy, Ranjana Patnaik
The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid after intranasal administration in Charles-Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path. The chlorogenic acid is administered intravenously (IV) and intranasally (IN) at the dose of 10 mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method. The study observes that chlorogenic acid is rapidly absorbed in plasma with tmax of 1 min similar to IV route after IN administration...
February 24, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Lauriane Goldwirt, Kevin Beccaria, Alain Ple, Hélène Sauvageon, Samia Mourah
PURPOSE: Central nervous system (CNS) dissemination occurs in 4.1% of mantle cell lymphoma (MCL) patients and clinically significant CNS involvement in chronic lymphocytic leukemia (CLL) patients reaches 4%. Ibrutinib, an orally administered Bruton's tyrosine kinase (BTK) inhibitor, has shown substantial activity in CLL or MCL patients with CNS localization, and in primary central nervous system lymphoma (PCNSL). The drug efficacy to treat primary or secondary CNS impairments relies on its brain distribution through the blood-brain barrier (BBB), the aim of the present work was to study the brain distribution of ibrutinib using an in vivo mice model...
February 23, 2018: Cancer Chemotherapy and Pharmacology
Ponnayyan Sulochana Suresh, Ravi Kumar Jairam, Devaraj V Chandrasekhar, Anera Balakrishna Vinod, Rakesh A Hiremath, Anusha Raj, Mohd Zainuddin, Ravi Kanth Bhamidipati, Ramesh Mullangi
BACKGROUND AND OBJECTIVES: Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. The primary objectives of the study were to evaluate the pharmacokinetics of ulixertinib in mice, rats, and dogs followed by prediction of human pharmacokinetic profile by allometric equations with/without correction factors. METHODS: Oral and intravenous pharmacokinetic profiles of ulixertinib were generated in mice, rats, and dogs. The human intravenous pharmacokinetics profiles [volume of distribution (Vss ) and clearance (CL)] were predicted employing simple allometry and using correction factors [maximum life span potential (MLP) and brain weight (BW)]...
February 22, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Chang Yell Shin, Hae-Sun Kim, Kwang-Ho Cha, Dong Han Won, Ji-Yun Lee, Sun Woo Jang, Uy Dong Sohn
A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately 1.2 ± 0.4 h and 1...
February 21, 2018: Biomolecules & Therapeutics
Jakob A Shimshoni, Eyal Sobol, Ezekiel Golan, Yulius Ben Ari, Orit Gal
5-Methoxy-2-aminoindane (MEAI) is a novel psychoactive aminoindane derivative, exerting euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. Our previous toxicological evaluation of MEAI in rats, clearly indicated MEAI's potential to be further evaluated as a promising binge mitigating agent due to its favorable safety profile. In the light of these observations, we have determined MEAI's pharmacokinetic (PK) profile in rats and evaluated in-vitro its pharmacodynamics (PD) profile...
February 16, 2018: Toxicology and Applied Pharmacology
Dorota Zolkowska, Chun-Yi Wu, Michael A Rogawski
Allopregnanolone (5α-pregnan-3α-ol-20-one) and its synthetic 3β-methyl analog, ganaxolone, are positive allosteric modulators of synaptic and extrasynaptic γ-aminobutyric acid (GABA)A receptors that exhibit antiseizure activity in diverse animal seizure models, including models of status epilepticus (SE). The 2 neuroactive steroids are being investigated as treatments for SE, including as a treatment for SE induced by chemical threat agents. Intramuscular injection is the preferred route of administration in the prehospital treatment of SE...
February 17, 2018: Epilepsia
Willem Johan van den Brink, Semra Palic, Isabelle Köhler, Elizabeth Cunera Maria de Lange
Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multiple pathways implicated in emotion and cognition, psychomotor functions and endocrine control through activation of G protein-coupled dopamine receptors. This review focuses on the system-wide effects of dopaminergic agents on the multiple biochemical and endocrine pathways, in particular the biomarkers (i...
February 15, 2018: Pharmaceutical Research
William M Pardridge, Ruben J Boado, Roberto Giugliani, Mathias Schmidt
BACKGROUND: Mucopolysaccharidosis type I (MPSI) is caused by mutations in the gene encoding the α-L-iduronidase (IDUA) lysosomal enzyme and the majority of MPSI patients have severe central nervous system (CNS) involvement. Enzyme replacement therapy (ERT) with recombinant IDUA does not treat the CNS, due to the lack of transport of the enzyme across the blood-brain barrier (BBB). Human IDUA has been re-engineered as an IgG-IDUA fusion protein, valanafusp alpha, where the IgG domain is a monoclonal antibody (MAb) against the human insulin receptor (HIR)...
February 13, 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Lopamudra Dutta, Biswajit Mukherjee, Tapash Chakraborty, Malay Kumar Das, Laboni Mondal, Sanchari Bhattacharya, Raghuvir H Gaonkar, Mita Chatterjee Debnath
Delivering highly water soluble drugs across blood-brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB...
November 2018: Drug Delivery
Yan-Fang Yang, You-Bo Zhang, Zhi-Jing Chen, Ying-Tao Zhang, Xiu-Wei Yang
BACKGROUND: The fruit of Psoralea corylifolia L., Psoraleae fructus (PF), is widely used in traditional Chinese medicine as a well-known herbal tonic. Previous studies have shown that PF and its major constituents may have potential values in the treatment of Parkinson and Alzheimer diseases, though their pharmacokinetics and brain distribution were largely unknown. PURPOSE: To develop a liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for simultaneous studies of the plasma pharmacokinetics and cerebral nuclei (including cerebellum, thalamus, brainstem, hippocampus, corpus striatum and cortex) distribution in rats of eleven known PF compounds following as psoralen, isopsoralen, psoralidin, bavachin, bavachinin, isobavachin, isobavachalcone, bavachalcone, neobavaisoflavone, corylifol A, and corylin...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Shahnaz Alimardani, Sima Sadrai, Hamidreza Taghvaye Masoumi, Pooneh Salari, Atabak Najafi, Behzad Eftekhar, Mojtaba Mojtahedzadeh
Objective: Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI). Methods: This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures...
October 2017: Journal of Research in Pharmacy Practice
Tae Hwan Kim, Soyoung Shin, Sun Dong Yoo, Beom Soo Shin
Pungent spice constituents such as piperine, capsaicin and [6]-gingerol consumed via daily diet or traditional Chinese medicine, have been reported to possess various pharmacological activities. These dietary phytochemicals have also been reported to inhibit P-glycoprotein (P-gp) in vitro and act as an alternative to synthetic P-gp modulators. However, the in vivo effects on P-gp inhibition are currently unknown. This study aimed to test the hypothesis that phytochemical P-gp inhibitors, i.e., piperine, capsaicin and [6]-gingerol, modulate the in vivo tissue distribution of doxorubicin, a representative P-gp substrate...
February 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S Grassin-Delyle, O M Theusinger, R Albrecht, S Mueller, D R Spahn, S Urien, P Stein
Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling...
February 7, 2018: Anaesthesia
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