journal
MENU ▼
Read by QxMD icon Read
search

Xenobiotica; the Fate of Foreign Compounds in Biological Systems

journal
https://www.readbyqxmd.com/read/30394160/in-vitro-inhibition-of-human-nucleoside-transporters-and-uptake-of-azacitidine-by-an-isocitrate-dehydrogenase-2-inhibitor-enasidenib-and-its-metabolite-agi-16903
#1
Zeen Tong, Usha Yerramilli, Sylvia Yao, James D Young, Matthew Hoffmann, Sekhar Surapaneni
1. The present study investigated inhibitory effects of enasidenib and its metabolite AGI-16903 on (a) recombinant human nucleoside transporters (hNTs) in hNT-producing Xenopus laevis oocytes, and (b) azacitidine uptake in normal B-lymphoblast peripheral blood cell line (PBC) and acute myeloid leukemia (AML) cell lines. 2. Enasidenib inhibited hENT1, hENT2, hENT3 and hENT4 in oocytes with IC50 values of 7, 63, 27 and 76 μM, respectively, but exhibited little inhibition of hCNT1-3. AGI-16903 exhibited little inhibition of any hNT produced in oocytes...
November 5, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30392427/kinetics-of-dextromethorphan-o-demethylase-activity-and-distribution-of-cyp2d-in-four-commonly-used-subcellular-fractions-of-rat-brain
#2
Barent N DuBois, Farideh Amirrad, Reza Mehvar
1. The purpose of this study was to compare the enzymatic kinetics and distribution of cytochrome P450 2D (CYP2D) among different rat brain subcellular fractions. 2. Rat brains were used to prepare total membrane, crude mitochondrial, purified mitochondrial, and microsomal fractions, in addition to total homogenate. Michaelis-Menten kinetics of the brain CYP2D activity was estimated based on the conversion of dextromethorphan (DXM) to dextrorphan using UPLC-MS/MS. Protein levels of CYP2D and subcellular markers were determined by Western blot...
November 5, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30240283/qspr-modelling-of-in-vitro-degradation-half-life-of-acyl-glucuronides
#3
Gulcin Tugcu, Hande Sipahi
Acyl glucuronidation is an important Phase II biotransformation, which is an efficient detoxification mechanism for the metabolism of carboxylic acid group-containing drugs. However, the reactivity of acyl glucuronide (AG) metabolites associated with short half-lives may be an indication of idiosyncratic drug toxicity. The degradation half-lives of AGs elucidate several important reactions such as hydrolysis, acyl migration and covalent binding to proteins. Prediction of degradation half-life using computational methods is a promising alternative approach to costly and time-consuming experiments, enabling a priori evaluation of the properties of drug candidates during the drug design process...
October 29, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30351217/novel-variants-and-haplotypes-of-human-flavin-containing-monooxygenase-3-fmo3-gene-associated-with-japanese-subjects-suffering-from-trimethylaminuria
#4
Makiko Shimizu, Hiromi Yoda, Narumi Igarashi, Miki Makino, Emi Tokuyama, Hiroshi Yamazaki
1. Flavin-containing monooxygenase 3 (FMO3) in humans is polymorphic in several ethnic groups, including Caucasians, Africans, and Asians. Some FMO3 variants are associated with a disorder trimethylaminuria. 2. In the current study, we used the results from urinary phenotyping assays to identify 63 subjects with <85% FMO3 metabolic capacity with respect to trimethylamine N-oxidation among 787 Japanese volunteers with self-reported trimethylaminuria. The 63 subjects with reduced FMO3 activity were screened and investigated in detail to identify novel FMO3 variants...
October 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30351213/comparative-toxicity-and-toxicokinetic-studies-of-oxiracetam-and-s-oxiracetam-in-dogs
#5
Tian-Tian Liu, Xin-Miao Guo, Zu-Yuan Rong, Xiang-Feng Ye, Jin-Feng Wei, Ai-Ping Wang, Hong-Tao Jin
1. Oxiracetam (ORT) is known as a derivative of piracetam in the family of nootropics for treating memory impairment and cognition disorders. 2. Given the chiral toxicological concerns surrounding ORT and the absence studies of (S)-ORT, the toxicity and toxicokinetics of (S)-ORT and comparative toxicology of oxiracetam, were systematically investigated in dogs following acute and 13-week repeated oral dosing. 3. The animal toxicity mainly manifested as loose stools in both the acute and the 13-week studies...
October 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30351210/biotransformation-of-anthocyanins-from-vitis-amurensis-rupr-of-beibinghong-extract-by-human-intestinal-microbiota
#6
Fei Zheng, Mingxin Han, Yang He, Yan Zhang, Shuying Liu, Hao Yue, Liankui Wen
1. Anthocyanins (ACNs) are a subclass of polyphenolic pigments belonging to the flavonoids and constitute an important group of human diets. There is accumulated evidence that consumption of ACN-rich diets such as Vitis Amurensis Rupr of "Beibinghong" exerts protective activities against some human diseases. These beneficial properties may be due to the biotransformation by intestinal microbiota and its related bacterial dependent metabolism of ACNs. However, despite the compositional characterization of ACNs in extracts from V...
October 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30351180/absorption-distribution-metabolism-and-excretion-of-radiolabeled-naldemedine-in-healthy-subjects
#7
Shuichi Ohnishi, Kazuya Fukumura, Ryuji Kubota, Toshihiro Wajima
1. Naldemedine is a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation. 2. This phase 1 study investigated the absorption, distribution, metabolism, and excretion of naldemedine, following a single oral 2-mg dose of [oxadiazole-14 C]-naldemedine or [carbonyl-14 C]-naldemedine to 12 healthy adult male subjects. Pharmacokinetic assessments were performed on blood, urine, and fecal samples collected at defined intervals. 3. Naldemedine was the major circulating component in plasma with a median Tmax of approximately 0...
October 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30351177/comprehensive-preclinical-pharmacokinetic-evaluations-of-trastuzumab-deruxtecan-ds-8201a-a-her2-targeting-antibody-drug-conjugate-in-cynomolgus-monkeys
#8
Yoko Nagai, Masataka Oitate, Hideyuki Shiozawa, Osamu Ando
1. Trastuzumab deruxtecan (DS-8201a) is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) conjugated to a topoisomerase I inhibitor (DXd) at a drug-to-antibody ratio (DAR) of 7-8. Here, we examined the pharmacokinetic (PK) profiles of DS-8201a and DXd in cynomolgus monkeys, a cross-reactive species. 2. Following intravenous (iv) administration of DS-8201a, the linker was stable in plasma, and systemic DXd exposure was low. DXd was rapidly cleared following iv dosing...
October 23, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30346892/antiretroviral-concentrations-and-surrogate-measures-of-efficacy-in-the-brain-tissue-and-csf-of-preclinical-species
#9
Nithya Srinivas, Elias P Rosen, William M Gilliland, Martina Kovarova, Leila Remling-Mulder, Gabriela De La Cruz, Nicole White, Lourdes Adamson, Amanda P Schauer, Craig Sykes, Paul Luciw, J Victor Garcia, Ramesh Akkina, Angela Dm Kashuba
1. Antiretroviral concentrations in cerebrospinal fluid (CSF) are used as surrogate for brain tissue, although sparse data support this. We quantified antiretrovirals in brain tissue across preclinical models, compared them to CSF, and calculated 90% inhibitory quotients (IQ90 ) for nonhuman primate (NHP) brain tissue. Spatial distribution of efavirenz was performed by mass-spectrometry imaging (MSI). 2. HIV or RT-SHIV-infected and uninfected animals from two humanized mouse models (hemopoietic-stem cell/RAG2-, n = 36; bone marrow-liver-thymus/BLT, n = 13) and an NHP model (rhesus macaque, n = 18) were dosed with six antiretrovirals...
October 22, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30328361/acetaminophen-is-both-bronchodilatory-and-bronchoprotective-in-human-precision-cut-lung-slice-airways
#10
Joshua L Kennedy, Richard C Kurten, Sandra McCullough, Reynold A Panettieri, Cynthia Koziol-White, Stacie M Jones, Katherine Caid, Pritmohinder S Gill, Dean Roberts, Hartmut Jaeschke, Mitchell R McGill, Laura James
INTRODUCTION: Epidemiologic studies have demonstrated an association between acetaminophen (APAP) use and the development of asthma symptoms. However, few studies have examined relationships between APAP-induced signaling pathways associated with the development of asthma symptoms. We tested the hypothesis that acute APAP exposure causes airway hyper-responsiveness (AHR) in human airways. METHODS: Precision cut lung slice (PCLS) airways from humans and mice were used to determine the effects of APAP on airway bronchoconstriction and bronchodilation and to assess APAP metabolism in lungs...
October 17, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30182817/effect-of-epigallocatechin-3-gallate-on-the-pharmacokinetics-of-amlodipine-in-rats
#11
Xiuyuan Han, Haixia Zhang, Huihui Hao, Hangao Li, Xichun Guo, Dong Zhang
This study investigates the effect of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, on the pharmacokinetics of amlodipine in rats. The pharmacokinetics of orally administered amlodipine (1 mg/kg) with or without EGCG pretreatment (30 mg/kg/day for 10 days) were investigated. Plasma concentrations of amlodipine were determined by using a sensitive and reliable liquid chromatography with tandem mass spectroscopy (LC-MS/MS) method. The effects of EGCG on the metabolic stability of amlodipine were investigated by using rat liver microsome incubation systems...
October 16, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30301406/phase-i-and-phase-ii-metabolism-simulation-of-antitumor-active-2-hydroxyacridinone-with-electrochemistry-coupled-on-line-with-mass-spectrometry
#12
Agnieszka Potęga, Dorota Garwolińska, Anna M Nowicka, Michał Fau, Agata Kot-Wasik, Zofia Mazerska
1. Here, we report the metabolic profile and the results of associated metabolic studies of 2-hydroxyacridinone (2-OH-AC), the reference compound for antitumor-active imidazo- and triazoloacridinones. 2. Electrochemistry coupled with mass spectrometry was applied to simulate the general oxidative metabolism of 2-OH-AC for the first time. The reactivity of 2-OH-AC products to biomolecules was also examined. The usefulness of the electrochemistry for studying the reactive drug metabolite trapping (conjugation reactions) was evaluated by the comparison with conventional electrochemical (controlled-potential electrolysis) and enzymatic (microsomal incubation) approaches...
October 10, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30301385/physiologically-based-pharmacokinetic-modeling-for-mirabegron-a-multi-elimination-pathway-mediated-by-cytochrome-p450-3a4-uridine-5-diphosphate-glucuronosyltransferase-2b7-and-butyrylcholinesterase
#13
Kentaro Konishi, Tsuyoshi Minematsu, Yasuhisa Nagasaka, Kenji Tabata
1. This was the first study to construct a physiologically-based pharmacokinetic (PBPK) model for mirabegron which incorporates the overall elimination pathways of metabolism by cytochrome P450 (CYP) 3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE) and renal excretion. The objective was to assess the risk of drug-drug interactions (DDIs) by estimating the contribution of each elimination pathway and simulating the magnitude of the DDIs with UGT2B7 inhibitors. 2...
October 10, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30299189/preclinical-pharmacokinetics-of-a-novel-anti-c-met-antibody-drug-conjugate-shr-a1403-in-rodents-and-non-human-primates
#14
Changyong Yang, Xiaoping Zhao, Xing Sun, Jinlong Li, Weiqiang Wang, Lianshan Zhang, Shaohua Gou
1. The in vivo pharmacokinetics (PK) profiles of a novel c-Met antibody-drug conjugate (ADC), SHR-A1403, were investigated and characterized in mice, rats and monkeys. 2. Serum concentrations of ADC and total antibody were detected using validated ELISA methods. The results showed low systemic clearance of both ADC and total antibody in all three species as reflected by gradual decrease in serum concentrations. Half-life (t1/2 ) of ADC ranged from 4.6 to 11.3 days in the three species. 3. Tissue distribution study in tumor-bearing mice showed high accumulation of 125 I-SHR-A1403 in tumor tissues over the other organs/tissues, indicating the favourable safety of SHR-A1403 and characteristics of an ADC drug...
October 9, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30286676/pharmacokinetic-study-of-the-prokinetic-abcs-liquiritigenin-naringenin-and-hesperitin-following-the-oral-administration-of-si-ni-san-decoction-to-functional-dyspepsia-patients
#15
Xi Huang, Jianjun Xu, Juan He, Shaoqi Shi, Hongbin Yan, Jian Wang, Ping Ren
1. The pharmacokinetics (PKs) analysis of compounds absorbed after the oral administration of Si-Ni-San (SNS) decoction to functional dyspepsia (FD) patients was designed to detect whether the effects were similar to prokinetics administered to healthy rats, without ethical limitation. 2. First, the absorbed compounds, liquiritigenin (L), naringenin (N) and hesperitin (H) in the plasma were identified by UPLC-MS/MS following the oral administration of SNS decoction to subjects with FD. Next, the natural ratio of LNH in the SNS decoction was determined by UPLC...
October 5, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29969338/expression-and-inducibility-of-cytochrome-p450s-in-human-hepatocytes-isolated-from-chimeric-mice-with-humanised-livers
#16
Shotaro Uehara, Yuichiro Higuchi, Nao Yoneda, Hiroshi Yamazaki, Hiroshi Suemizu
The evaluation of drug-mediated cytochrome P450 (P450) induction using human hepatocytes is important for predicting drug interactions. In this study, we prepared hepatocytes from chimeric mice with humanised livers (Hu-Liver mice) and evaluated the expression and inducibility of P450s in these hepatocytes. Up to 95% of the Hu-Liver cells stained positive for human leukocyte antigen and the mean viability exceeded 85% (n = 10). Monolayer-cultured Hu-Liver cells displayed a similar morphology to cultures of the corresponding human hepatocytes used as transplantation donors...
October 4, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30272491/development-of-new-coumarin-based-profluorescent-substrates-for-human-cytochrome-p450-enzymes
#17
Risto O Juvonen, Mira Ahinko, Juhani Huuskonen, Hannu Raunio, Olli T Pentikäinen
1. Cytochrome P450 (CYP) enzymes constitute an essential xenobiotic metabolizing system that regulates the elimination of lipophilic compounds from the body. Convenient and affordable assays for CYP enzymes are important for assessing these metabolic pathways. 2. In this study, 10 novel profluorescent coumarin derivatives with various substitutions at carbons 3, 6 and 7 were developed. Molecular modeling indicated that 3-phenylcoumarin offers an excellent scaffold for the development of selective substrate compounds for various human CYP forms, as they could be metabolized to fluorescent 7-hydroxycoumarin derivatives...
October 1, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30044681/in-vitro-and-in-vivo-pharmacokinetic-characterization-of-mavacamten-a-first-in-class-small-molecule-allosteric-modulator-of-beta-cardiac-myosin
#18
Mark P Grillo, John C L Erve, Ryan Dick, James P Driscoll, Nicole Haste, Svetlana Markova, Priscilla Brun, Timothy J Carlson, Marc Evanchik
Mavacamten is a small molecule modulator of cardiac myosin designed as an orally administered drug for the treatment of patients with hypertrophic cardiomyopathy. The current study objectives were to assess the preclinical pharmacokinetics of mavacamten for the prediction of human dosing and to establish the potential need for clinical pharmacokinetic studies characterizing drug-drug interaction potential. Mavacamten does not inhibit CYP enzymes, but at high concentrations relative to anticipated therapeutic concentrations induces CYP2B6 and CYP3A4 enzymes in vitro...
October 1, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30257601/preclinical-assessment-of-the-adme-efficacy-and-drug-drug-interaction-potential-of-a-novel-nampt-inhibitor
#19
Bianca M Liederer, Jonathan Cheong, Kang-Jye Chou, Peter S Dragovich, Hoa Le, Xiaorong Liang, Justin Ly, Sophie Mukadam, Jason Oeh, Deepak Sampath, Leslie Wang, Susan Wong
1. GNE-617 (N-(4-((3,5-difluorophenyl)sulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide) is a potent, selective nicotinamide phosphoribosyltransferase (NAMPT) inhibitor being explored as a potential treatment for human cancers. 2. Plasma clearance was low in monkeys and dogs (9.14 mL min-1 kg-1 and 4.62 mL min-1 kg-1 , respectively) and moderate in mice and rats (36.4 mL min-1 kg-1 and 19.3 mL min-1 kg-1 , respectively). Oral bioavailability in mice, rats, monkeys and dogs was 29.7, 33.9, 29.4 and 65...
September 26, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/30257131/disposition-of-fullerene-c60-in-rats-following-intratracheal-or-intravenous-administration
#20
K A Shipkowski, J M Sanders, J D McDonald, N J Walker, S Waidyanatha
1. Fullerene C60 is used in a variety of industrial and consumer capacities. As part of a comprehensive evaluation of the toxicity of fullerene C60 by the National Toxicology Program, the disposition following intratracheal (IT) instillation and intravenous (IV) administration of 1 or 5 mg/kg b.wt. fullerene C60 was investigated in male Fischer 344 rats. 2. Following IT instillation, fullerene C60 was detected in the lung as early as 0.5 h post-exposure with minimal clearance over the 168 h period; the concentration increased ≥ 20-fold with a 5-fold increase in the dose...
September 26, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
journal
journal
25459
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"