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pharmacokinetics, brain, plasma

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https://www.readbyqxmd.com/read/28324653/evaluation-of-brain-pharmacokinetic-and-neuropharmacodynamic-attributes-of-antiepileptic-drug-lacosamide-in-hepatic-and-renal-impairment-preclinical-evidence
#1
Baldeep Kumar, Manish Modi, Biman Saikia, Bikash Medhi
The knowledge of pharmacokinetic and pharmacodynamic properties of antiepileptic drugs is helpful in optimizing drug therapy for epilepsy. This study was designed to evaluate the pharmacokinetic and pharmacodynamic properties of lacosamide in experimentally induced hepatic and renal impairment in seizure animals. Hepatic or renal impairment was induced by injection of carbon tetrachloride or diclofenac sodium, respectively. After induction, the animals were administered with a single dose of lacosamide. At different time points, MES seizure recordings were done followed by isolation of plasma and brain samples for drug quantification and pharmacodynamic measurements...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#2
Jessica Raper, J Scott Daniels, Ryan D Morrison, Leonard Howell, Jocelyne Bachevalier, Thomas Wichmann, Adriana Galvan
The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies, but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28298024/reduction-of-inflammation-after-administration-of-interleukin-1-receptor-antagonist-following-aneurysmal-subarachnoid-hemorrhage-results-of-the-subcutaneous-interleukin-1ra-in-sah-scil-sah-study
#3
James Galea, Kayode Ogungbenro, Sharon Hulme, Hiren Patel, Sylvia Scarth, Margaret Hoadley, Karen Illingworth, Catherine J McMahon, Nikolaos Tzerakis, Andrew T King, Andy Vail, Stephen J Hopkins, Nancy Rothwell, Pippa Tyrrell
OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular event with long-term morbidity and mortality. Patients who survive the initial bleeding are likely to suffer further early brain injury arising from a plethora of pathological processes. These may result in a worsening of outcome or death in approximately 25% of patients and may contribute to longer-term cognitive dysfunction in survivors. Inflammation, mediated by the cytokine interleukin-1 (IL-1), is an important contributor to cerebral ischemia after diverse forms of brain injury, including aSAH...
February 24, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28291630/ceftriaxone-pharmacokinetics-by-new-simple-and-sensitive-ultra-high-performance-liquid-chromatography-method
#4
Michel Leandro Campos, Juliana de Moura Alonso, Evelin Dos Santos Martins, Jonata Augusto Oliveira, Carlos Alberto Hussni, Rosângela Gonçalves Peccinini
Ceftriaxone is a cephalosporin antibiotic with a potent antimicrobial activity and excellent penetration in most body fluids such as pleural, peritoneal, spinal and brain. These facts contribute to the application of ceftriaxone in the treatment of bacterial peritonitis, an abdominal disorder in veterinary medicine, with potential risk of death. The determination of ceftriaxone levels in plasma and peritoneal fluid may be used to assess the pharmacokinetic profile at various instances of administration and allows observing if the concentrations needed are being achieved...
February 27, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28290002/plasma-and-cerebrospinal-fluid-pharmacokinetics-of-select-chemotherapeutic-agents-following-intranasal-delivery-in-a-non-human-primate-model
#5
James C League-Pascual, Cynthia M Lester-McCully, Shaefali Shandilya, Lukas Ronner, Louis Rodgers, Rafael Cruz, Cody J Peer, William D Figg, Katherine E Warren
The blood-brain barrier (BBB) limits entry of most chemotherapeutic agents into the CNS, resulting in inadequate exposure within CNS tumor tissue. Intranasal administration is a proposed means of delivery that can bypass the BBB, potentially resulting in more effective chemotherapeutic exposure at the tumor site. The objective of this study was to evaluate the feasibility and pharmacokinetics (plasma and CSF) of intranasal delivery using select chemotherapeutic agents in a non-human primate (NHP) model. Three chemotherapeutic agents with known differences in CNS penetration were selected for intranasal administration in a NHP model to determine proof of principle of CNS delivery, assess tolerability and feasibility, and to evaluate whether certain drug characteristics were associated with increased CNS exposure...
March 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28285369/diclofenac-sex-divergent-drug-drug-interaction-with-sunitinib-pharmacokinetics-and-tissue-distribution-in-male-and-female-mice
#6
Chii Chii Chew, Salby Ng, Yun Lee Chee, Teng Wai Koo, Ming Hui Liew, Evelyn Li-Ching Chee, Pilar Modamio, Cecilia Fernández, Eduardo L Mariño, Ignacio Segarra
Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC0→∞ 38% in plasma (p < 0.05) and 24% in liver (p < 0.001) and 23% in kidney (p < 0...
March 11, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28277164/pharmacokinetics-of-the-selective-prostacyclin-receptor-agonist-selexipag-in-rats-dogs-and-monkeys
#7
Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber, Carmela Gnerre, Kiyoko Nonaka
1. This study examined the pharmacokinetics, distribution, metabolism and excretion of the selective prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-33679). The compounds were investigated following oral and/or intravenous administration to intact rats, dogs and monkeys, and bile-duct-cannulated rats and dogs. 2. After oral administration of [(14)C]selexipag, selexipag was well absorbed in rats and dogs with total recoveries of over 90% of the dose, mainly in the faeces...
March 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28257822/characterization-of-6-methoxyflavanone-as-a-novel-anxiolytic-agent-a-behavioral-and-pharmacokinetic-approach
#8
Shehla Akbar, Fazal Subhan, Nasiara Karim, Urooj Aman, Sami Ullah, Muhammad Shahid, Nisar Ahmad, Khwaja Fawad, Robert D E Sewell
Benzodiazepines are regularly prescribed for treatment of anxiety though there are side effects. Flavonoids have selective affinity for GABAA receptors implicated in anxiolytic-like activity in rodents, but are devoid of the unwanted side effects of benzodiazepines. In this study, 6-methoxyflavanone (6-MeOF), a positive allosteric modulator of γ-amino butyric acid (GABA) responses at human recombinant GABAA receptors, was evaluated for its behavioral profile in the elevated plus-maze as well as the staircase- plus and open-field tests in mice...
February 28, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28255523/inhibition-of-soluble-epoxide-hydrolase-as-a-novel-approach-to-high-dose-diazepam-induced-hypotension
#9
Arzu Ulu, Bora Inceoglu, Jun Yang, Vikrant Singh, Stephen Vito, Heike Wulff, Bruce D Hammock
CONTEXT: Hypotension is one of the dose limiting side effects of benzodiazepines (BZDs), in particular of diazepam (DZP) which is still widely used in the clinic. Currently, only one FDA approved antidote exists for BZD overdose and novel approaches are needed to improve management of DZP overdose, dependency and withdrawal. OBJECTIVE: Here, we hypothesized that increasing bioactive lipid mediators termed epoxy fatty acids (EpFAs) will prevent hypotension, as was shown previously in a murine model of LPS-induced hypotension...
June 2016: Journal of Clinical Toxicology
https://www.readbyqxmd.com/read/28245513/brain-translocator-protein-occupancy-by-ono-2952-in-healthy-adults-a-phase-1-pet-study-using-11-c-pbr28
#10
William G Frankle, Rajesh Narendran, Andrew T Wood, Fumitaka Suto, Michael L Himes, Michiyoshi Kobayashi, Tomoya Ohno, Akinori Yamauchi, Katsukuni Mitsui, Kevin Duffy, Bruce Mark
ONO-2952, a novel antagonist of translocator protein 18 kDa (TSPO), binds with high affinity to TSPO in rat brain and human tumor cell line membrane preparations. This study used the TSPO-specific PET radioligand [(11) C]PBR28 to confirm binding of ONO-2952 to brain TSPO in human subjects, and evaluate brain TSPO occupancy and its relationship with ONO-2952 plasma concentration. Sixteen healthy subjects received a single oral dose of 200, 60, 20, or 6 mg ONO-2952 (n=4 per dose). Two PET scans with [(11) C]PBR28 were conducted ≤7 days apart: at baseline and 24 hours after ONO-2952 administration...
February 28, 2017: Synapse
https://www.readbyqxmd.com/read/28238945/nose-to-brain-transport-of-imatinib-mesylate-a-pharmacokinetic-evaluation
#11
Nobuko Hada, William Joseph Netzer, Fanny Belhassan, Lawrence Paul Wennogle, Sveinbjörn Gizurarson
The delivery of drugs to the brain is a constant challenge due to limitations imposed by the blood-brain barrier (BBB). Various methods of bypassing the BBB are under investigation. One approach is intranasal administration, where the olfactory region of the nasal cavity extends up to the cranial cavity and provides direct access to the brain. The pharmacokinetics of this transport and factors that determine transport rates and capacity is of vital importance for evaluating the clinical value of this route...
February 24, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28213761/psychomotor-effect-differences-between-l-methamphetamine-and-d-methamphetamine-are-independent-of-murine-plasma-and-brain-pharmacokinetics-profiles
#12
Tetsuya Nishimura, Kazue Takahata, Yuri Kosugi, Takaaki Tanabe, Shizuko Muraoka
l-Methamphetamine has been occasionally referred to as a stimulant similar to d-methamphetamine, probably owing to insufficient comparative studies. Here, we directly compared psychomotor efficacies and pharmacokinetics of methamphetamine enantiomers in mice. Only d-methamphetamine, but not l-methamphetamine, induced stereotypy and sensitization at 1-10 mg/kg. However, plasma pharmacokinetic parameters of 10 mg/kg l-methamphetamine were ≥tenfold those of 1 mg/kg d-methamphetamine. These results clearly indicate that differential psychomotor efficacies of methamphetamine enantiomers are independent of their pharmacokinetic profiles...
February 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28213295/determination-of-imm-h004-a-novel-neuroprotective-agent-in-rat-plasma-and-brain-tissue-by-liquid-chromatography-tandem-mass-spectrometry
#13
Ziqian Zhang, Xiangmeng Wu, Manman Zhao, Yakun Yang, Yan Wang, Jinping Hu, Baolian Wang, Li Sheng, Yan Li
A rapid and sensitive liquid chromatography-tandem mass spectrometry method for determination of IMM-H004, a novel neuroprotective agent, in rat plasma and brain was developed. Plasma and brain tissue homogenate samples containing IMM-H004 and propranolol (internal standard, IS) were prepared by using a direct protein precipitation of acetonitrile. Separation was carried out in Zorbax SB-C18 column at a flow rate of 0.3mL/min utilizing acetonitrile/water as mobile phases which contain 0.5% formic acid (v/v)...
March 24, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28199114/curcumin-loaded-blood-stable-polymeric-micelles-for-enhancing-therapeutic-effect-on-erythroleukemia
#14
Feirong Gong, Dan Chen, Xin Teng, Junhua Ge, Xianfeng Ning, Ya-Ling Shen, Jian Li, Shanfeng Wang
Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy...
February 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28193520/mdr1a-plays-a-crucial-role-in-regulating-the-analgesic-effect-and-toxicity-of-aconitine-by-altering-its-pharmacokinetic-characteristics
#15
Lijun Zhu, Jinjun Wu, Min Zhao, Wenjie Song, Xiaoxiao Qi, Ying Wang, Linlin Lu, Zhongqiu Liu
Aconitine (AC) is the primary bioactive/toxic alkaloid in plants of the Aconitum species. Our previous study demonstrated that Mdr1 was involved in efflux of AC. However, the mechanism by which Mdr1 regulates the efficacy/toxicity of AC in vivo remains unclear. The present study aimed to determine the effects of Mdr1a on the efficacy/toxicity and pharmacokinetics of AC in wild-type and Mdr1a(-/-) FVB mice. After oral administration of AC, significantly higher analgesic effect was observed in Mdr1a(-/-) mice (49% to 105%) compared to wild-type mice (P<0...
February 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28192085/influence-of-peptide-transporter-2-pept2-on-the-distribution-of-cefadroxil-in-mouse-brain-a-microdialysis-study
#16
Xiaomei Chen, Richard F Keep, Yan Liang, Hao-Jie Zhu, Margareta Hammarlund-Udenaes, Yongjun Hu, David E Smith
Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a ß-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis...
February 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28190755/quantitative-prediction-of-histamine-h1-receptor-occupancy-by-the-sedative-and-non-sedative-antagonists-in-the-human-central-nervous-system-based-on-systemic-exposure-and-preclinical-data
#17
Kayoko Kanamitsu, Yoshitane Nozaki, Yoko Nagaya, Yuichi Sugiyama, Hiroyuki Kusuhara
Significant histamine H1 receptor occupation in the central nervous system (CNS) is associated with sedation. Here we examined the time profiles of the H1 receptor occupancy (RO) in the CNS using sedative (diphenhydramine and ketotifen) and non-sedative (bepotastine and olopatadine) antagonists at their therapeutic doses by integrating in vitro and animal data. A pharmacokinetic model was constructed to associate plasma concentrations and receptor binding in the brain. Dissociation and association rate constants with the H1 receptor and plasma and brain unbound fractions were determined in vitro...
November 18, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28178362/determination-of-the-neuropharmacological-drug-nodakenin-in-rat-plasma-and-brain-tissues-by-liquid-chromatography-tandem-mass-spectrometry-application-to-pharmacokinetic-studies
#18
Yingshi Song, Huiyu Yan, Jingbo Xu, Hongxi Ma
A rapid and sensitive liquid chromatography tandem mass spectrometry detection using SRM in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid-liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2...
February 8, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28167558/pharmacokinetic-and-tissue-distribution-of-benznidazole-after-oral-administration-in-mice
#19
Luísa Perin, Rodrigo Moreira da Silva, Kátia da Silva Fonseca, Jamille Mirelle de Oliveira Cardoso, Fernando Augusto Siqueira Mathias, Levi Eduardo Soares Reis, Israel Molina, Rodrigo Correa-Oliveira, Paula Melo de Abreu Vieira, Cláudia Martins Carneiro
Specific chemotherapy using Benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) method was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquid-liquid extraction using ethyl acetate...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28165806/enhancing-both-oral-bioavailability-and-brain-penetration-of-puerarin-using-borneol-in-combination-with-preparation-technologies
#20
Tao Yi, Dandan Tang, Fan Wang, Jiqiong Zhang, Jiao Zhang, Jirui Wang, Xiaoyu Xu, Jifen Zhang
Now there are few good oral preparations of puerarin used in cerebrovascular diseases because of its poor oral absorption caused by the low water solubility and the poor penetration into brain. In this study, three oral formulations of puerarin, nanocrystals suspension (NCS), inclusion compounds solution (ICS) and self-microemulsifying drug delivery system (SMEDDS) were prepared with borneol as an oral brain-targeting enhancer. A rat syngeneic in vitro model of the brain-blood barrier (BBB) was established to investigate effects of borneol on the permeability of puerarin across the BBB...
November 2017: Drug Delivery
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