journal
MENU ▼
Read by QxMD icon Read
search

Xenobiotica; the Fate of Foreign Compounds in Biological Systems

journal
https://www.readbyqxmd.com/read/29165024/evaluation-of-separate-role-of-intestine-and-liver-in-first-pass-metabolism-of-budesonide-in-rat
#1
Amol A Raje, Radni D Deshpande, Vishal V Pathade, Vallabh Mahajan, Kaushal Joshi, Ashwini Tambe, Ramana Jinugu, Vamsi L M Madgula, Ashwani Gaur, Vishwottam Kandikere, Chandragouda R Patil, Kasim A Mookhtiar
1. Budesonide, a potent topical corticosteroid, reported to have low oral bioavailability in mice, rat, dog and human due to rapid first pass metabolism. However, there is insufficient information available in literature regarding the role of intestine and or liver responsible for the first pass metabolism of budesonide. 2. Current study in rats investigates the role of intestine and liver in first pass metabolism of budesonide using two in vivo models. Additionally, budesonide was also evaluated in in vitro assays such as thermodynamic solubility, permeability in Caco-2 cells and stability in simulated gastric (SGF), intestinal fluids (SIF) to understand the underlaying cause for low oral bioavailability...
November 22, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29160763/efficient-brain-uptake-of-piperine-and-its-pharmacokinetics-characterization-after-oral-administration
#2
Tianjing Ren, Qianwen Wang, Chenrui Li, Mengbi Yang, Zhong Zuo
1. Piperine, the major biological active component in black pepper has been associated with miscellaneous pharmacological effects, especially on central nervous system. To correlates with its neurological activity, a comprehensive pharmacokinetic profile of piperine in brain, plasma and cerebrospinal fluid after oral administration in rats was investigated in the current study. 2. It was noted that piperine could efficiently penetrate and homogeneously distribute into brain with similar pharmacokinetics profiles in each region...
November 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29160126/leishmanicidal-candidate-lassbio-1736-a-cysteine-protease-inhibitor-with-favorable-pharmacokinetics-low-clearance-and-good-distribution
#3
Barbra Sanches Moraes, Francine Johansson Azeredo, Jessica Cristina Izoton, Marina Amaral, Eliezer de Jesus Barreiro, Rodrigo José Freddo, Teresa Dalla Costa, Lídia Moreira Lima, Sandra Elisa Haas
1. LASSBio-1736 ((E)-1-4(trifluoromethyl) benzylidene)-5-(2-4-dichlorozoyl) carbonylhydrazine) is proposed to be an oral cysteine protease leishmanicidal inhibitor. 2. This work aimed to investigate plasma pharmacokinetics, protein binding and tissue distribution of LASSBio-1736 in male Wistar rats. 3. LASSBio-1736 was administered to male Wistar rats at doses of 3.2 mg/kg intravenously and 12.6 mg/kg oral and intraperitoneal. The individual plasma-concentration profiles were determined by HPLC-UV and evaluated by non-compartmental and population pharmacokinetic analysis (Monolix 2016R1, Lixoft)...
November 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29160125/effects-of-paeoniflorin-on-the-activities-and-mrna-expression-of-rat-cyp1a2-cyp2c11-and-cyp3a1-enzymes-in-vivo
#4
Sicong Li, Xuting Li, Dingsheng Yuan, Bin Wang, Rui Yang, Min Zhang, Jinliang Li, Fuqiang Zeng
1. Paeoniflorin is the major constituent in extracts of the peony root, the purpose of the present study was to assess the effects of paeoniflorin on the activities and mRNA expression of the rat hepatic drug-metabolizing enzymes cytochrome P450 (CYP1A2), CYP2C11 and CYP3A1 in vivo. 2. Sprague-Dawley (SD) male rats were treated with paeoniflorin at the dosage of 25, 50 and 100 mg/kg or 0.9% sodium chloride solution by intragastric administration for 7 days, then were given probe drugs phenacetin (CYP1A2), tolbutamide (CYP2C11), or midazolam (CYP3A1) orally on the eighth day...
November 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29157071/metabolism-of-metofluthrin-in-rats-ii-excretion-distribution-and-amount-of-metabolites
#5
Jun Abe, Yoshitaka Tomigahara, Hirokazu Tarui, Hirohisa Nagahori, Motohiro Kurosawa, Kenji Sugimoto, Naohiko Isobe
1. (14 )C-Labelled E/Z isomers of a synthetic pyrethroid metofluthrin ((E/Z)-(1 R,3 R)-2,3,5,6-tetrafluoro-4-(methoxymethyl)benzyl 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylate, abbreviated as RTE/RTZ, respectively) were used for rat metabolism studies. (14 )C-RTE or RTZ labelled at the carbonyl-carbon [acid-(14)C] or the methoxymethylbenzyl-α-carbon [alcohol-(14 )C] was administered orally to rats at 1 and 20 mg/kg. 2. Dosed compounds were mostly absorbed, metabolised, and rapidly excreted...
November 20, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29143555/qualitative-and-quantitative-prediction-of-human-in-vivo-metabolic-pathways-in-a-human-hepatocyte-murine-stromal-cell-co-culture-model
#6
Kenneth C Cassidy, Ping Yi
1. This study assessed the value of a static in vitro human hepatocyte-murine stromal cell co-culture model to qualitatively and quantitatively predict human in vivo metabolic clearance pathways using (14)C-labeled test compounds and compared these results to an in vitro suspended human hepatocyte model and the in vivo human (14)C ADME studies. 2. Test compounds represented a diverse set of clearance pathways (Phase I and Phase II). Compounds were incubated for 4 h in suspended human hepatocytes and for 24 and 168 h in the human co-culture model...
November 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29143552/metabonomics-analysis-of-serum-from-rats-given-long-term-and-low-level-cadmium-by-ultra-performance-liquid-chromatography-mass-spectrometry
#7
Liyan Hu, Lu Bo, Meiyan Zhang, Siqi Li, Xiujuan Zhao, Changhao Sun
1. This study evaluated the toxicity of chronic exposure to low-level cadmium (Cd) in rats using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Forty male Sprague-Dawley rats were randomly assigned to four groups, namely, the control group, low-dose group (0.13 mg/kg·bw), middle-dose group (0.8 mg/kg·bw) and high-dose group (4.89 mg/kg·bw). The rats continuously received CdCl2 via drinking water for 24 weeks. Serum samples were collected for metabonomics analysis. The data generated from the UPLC-MS was analysed using principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA)...
November 16, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29111853/metabolism-and-disposition-of-2-ethylhexyl-p-methoxycinnamate-following-oral-gavage-and-dermal-exposure-in-harlan-sprague-dawley-rats-and-b6c3f1-n-mice-and-in-hepatocytes-in-vitro
#8
Timothy R Fennell, James M Mathews, Rodney W Snyder, Yang Hong, Scott L Watson, Sherry R Black, Barry S McIntyre, Suramya Waidyanatha
1. 2-Ethylhexyl-p-methoxycinnamate (EHMC) is commonly used as an ingredient in sunscreens, resulting in potential oral and dermal exposure in humans. 2. Clearance and metabolism of EHMC in hepatocytes and disposition and metabolism of EHMC in rodents following oral (8 to 800 mg/kg) intravenous (IV) (8 mg/kg), or dermal (0.8 to 80 mg/kg representing 0.1 to 10% formulation concentration) exposure to [(14)C]EHMC were investigated in rats and mice. 3. EHMC was rapidly cleared from rat and mouse hepatocytes (half-life ≤ 3...
November 7, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29105555/toxicity-of-new-synthetic-amphetamine-drug-mephedrone-on-rat-heart-mitochondria-a-warning-for-its-abuse
#9
Parvaneh Naserzadeh, Farzaneh Jokar, Farzaneh Vafaei, Enayatollah Seydi, Jalal Pourahmad
1. Mephedrone, a new and popular amphetamine drug, is widely abused and is still legal in some parts around the world. Little data on mechanisms involved in mephedrone induced cardiotoxicity are available. 2. Therefore, we decided to explain the mechanisms of mephedrone cardiotoxicity by using mitochondria isolated from rat heart. The isolated heart mitochondria were incubated with different concentrations of mephedrone (5, 10 and 20 µM). 3. Results showed that mephedrone induced mitochondrial dysfunction via an increase in mitochondrial reactive oxygen species (ROS) production, MMP collapse, mitochondrial swelling and damage in the mitochondrial outer membrane (MOM) which is associated with the cytochrome c release...
November 6, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29099639/effects-of-glycyrrhizin-on-the-pharmacokinetics-of-puerarin-in-rats
#10
Qun Zhao, Yingli Wang, Hongqin Wang, Lichun Feng
1. Puerarin has been reported to possess a wide range of pharmacological activities. This study investigated the effects of glycyrrhizin on the pharmacokinetics of puerarin in rats. 2. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day for 7 days) were investigated. The plasma concentration of puerarin was determined using a sensitive and reliable LC-MS/MS method. The pharmacokinetics profiles were calculated and compared. Additionally, a Caco-2 cell transwell model was used to investigate the potential mechanism of glycyrrhizin's effects on the pharmacokinetics of puerarin...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29098941/efflux-transporter-breast-cancer-resistance-protein-dominantly-expresses-on-the-membrane-of-red-blood-cells-hinders-partitioning-of-its-substrates-into-the-cells-and-alters-drug-drug-interaction-profiles
#11
Pu Shi, Mingxiang Liao, Bei-Ching Chuang, Robert Griffin, Judy Shi, Marc Hyer, John K Fallon, Philip C Smith, Chao Li, Cindy Q Xia
1. Red blood cell (RBC) partitioning is important in determining pharmacokinetic and pharmacodynamic properties of a compound; however, active transport across RBC membranes is not well understood, particularly without transporter-related cell membrane proteomics data. 2. In this study, we quantified breast cancer resistance protein (BCRP/Bcrp) and MDR1/P-glycoprotein (P-gp) protein expression in RBCs from humans, monkeys, dogs, rats, and mice using nanoLC/MS/MS, and evaluated their effect on RBC partitioning and plasma exposure of their substrates...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29098926/the-impact-of-sesquiterpenes-%C3%AE-caryophyllene-oxide-and-transnerolidol-on-xenobiotic-metabolizing-enzymes-in-mice-in-vivo
#12
Kateřina Lněničková, Hana Svobodová, Lenka Skálová, Martin Ambrož, Filip Novák, Petra Matoušková
1. Sesquiterpenes, constituents of plant essential oil, are popular bioactive compounds due to the positive effect on human health, but their potential toxicity and possible herb-drug interactions are often omitted. In our in vivo study, we followed up the effect of p.o. administration of two sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) on various xenobiotic-metabolizing enzymes in mice liver and small intestine. 2. To spot the early effect of studied compounds, enzymatic activity and mRNA levels were assessed 6 and 24 h after single dose...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29095659/indirect-activation-of-pregnane-x-receptor-in-the-induction-of-hepatic-cyp3a11-by-high-dose-rifampicin-in-mice
#13
Yuki Yamasaki, Kaoru Kobayashi, Asumi Inaba, Daisuke Uehara, Hiroki Tojima, Satoru Kakizaki, Kan Chiba
Rifampicin (RIF), a typical ligand of human pregnane X receptor (PXR), powerfully induces the expression of cytochrome P450 3A4 (CYP3A4) in humans. Although it is thought that RIF is not a ligand of rodent PXR, treatment with high-dose RIF (e.g., more than 20 mg/kg) increases the expression of CYP3A in the mouse liver. In this study, we investigated whether the induction of CYP3A by high-dose RIF in the mouse liver is mediated via indirect activation of mouse PXR (mPXR). The results showed that high-dose RIF increased the expression of CYP3A11 and other PXR-target genes in the liver of wild-type mice but not PXR-knockout mice...
November 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29092680/mass-balance-and-metabolism-of-z-215-a-novel-proton-pump-inhibitor-in-healthy-volunteers
#14
Ryoko Toda, Tomoharu Miyagawa, Yuka Masuda, Yusuke Hoshino, Kazuyoshi Yoshii, Masamichi Hirayama, Minaka Shibuya, Yoshihiro Kawabata
The human mass balance of [(14 )C]Z-215, a novel proton pump inhibitor, was characterised in six healthy male volunteers following single oral administration of [(14 )C]Z-215 (20 mg, 3.7 MBq) to determine the elimination pathway of Z-215 and the distribution of its metabolites in plasma, urine, and faeces (NCT02618629). [(14 )C]Z-215 was rapidly absorbed, with a Cmax of 434 ng/mL at 0.38 h for Z-215 and 732 ng eq./mL at 0.5 h for total radioactivity. Means of 59.61% and 31.36% of the administered radioactive dose were excreted in urine and faeces, respectively, within 168 h post-dose...
November 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29092654/changes-in-cyp2d-enzyme-activity-following-induction-of-type-2-diabetes-and-administration-of-cinnamon-and-metformin-an-experimental-animal-study
#15
Ali Taheri, Hoda Lavasani, Sara Kasirzadeh, Behjat Sheikholeslami, Yalda H Ardakani, Mohammad-Reza Rouini
1. Alterations in the activity of hepatic cytochrome P-450 isoenzymes result in changes in the pharmacokinetic behavior of drugs. This study was designed to explore the impact of type II diabetes, metformin and cinnamon on the activity of CYP2D isoenzyme. 2. Streptozotocin-nicotinamide-induced diabetic and normal rats were gavaged by cinnamon and/or metformin for 14 days. Using isolated perfusion of rat livers, the metabolic activity of CYP2D in the study groups was evaluated based on the oxidative biotransformation of tramadol hydrochloride...
November 2, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29082813/identification-and-analysis-of-the-reactive-metabolites-related-to-the-hepatotoxicity-of-safrole
#16
Ai-Hong Yang, Lei Zhang, De-Xian Zhi, Wen-Li Liu, Xue Gao, Xin He
1. Safrole is the main component of volatile oil in Xixin, which has a strong antifungal effect. However, safrole has been shown to be associated with the development of hepatocellular carcinoma. Methylenedioxyphenyl and allyl-benzene substructures of safrole may cause a mechanism-based inhibition (MBI) of CYP450 enzymes (CYPs) and produce reactive metabolites (RMs), resulting in inhibition of enzyme activity and toxic effects. 2. Based on the experiments of CYPs cocktail screening, GSH capture and the IC50 data, we found that safrole had an inhibitory effect on CYP1A2...
October 30, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29057719/changes-in-gefitinib-erlotinib-and-osimertinib-pharmacokinetics-under-various-gastric-ph-levels-following-oral-administration-of-omeprazole-and-vonoprazan-in-rats
#17
Osamu Yasumuro, Shinya Uchida, Yasuharu Kashiwagura, Ayae Suzuki, Shimako Tanaka, Naoki Inui, Hiroshi Watanabe, Noriyuki Namiki
1. Although drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and gastric acid-suppressing medications (AS) are considered clinically significant, there is limited data regarding the influence of various gastric pH conditions on the pharmacokinetics of EGFR-TKIs. We aimed to clarify the changes in the pharmacokinetics of the EGFR-TKIs, gefitinib, erlotinib, and osimertinib, due to the changes in gastric pH after administration of omeprazole or vonoprazan. 2. Omeprazole (10 - 100 mg/kg, p...
October 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29052493/impaired-liver-cytochrome-p450-2c11-activity-after-dual-antiplatelet-therapy-with-aspirin-and-clopidogrel-in-rats
#18
Chenyu Qian, Xi Luo, Mengbi Yang, Jing Jin, Zhong Zuo
1. Aspirin (ASA) and clopidogrel (CLP) are used in combination as dual antiplatelet therapy (DAPT) for acute coronary syndrome based on their complementary mechanisms for platelet aggregation inhibition. However, the pharmacokinetics of such drug combination usage has not been thoroughly investigated. 2. In the current study, an LC-MS/MS method was developed to simultaneously determine the plasma concentrations of ASA and its metabolite salicylic acid (SA) with CLP and its metabolites, clopidogrel carboxylic acid (CLPM) and clopidogrel active metabolite derivative (CAMD)...
October 20, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29050522/metabolism-of-megestrol-acetate-in-vitro-and-the-role-of-oxidative-metabolites
#19
Larry House, Michael Seminerio, Snezana Mirkov, Jacqueline Ramirez, Maxwell Skor, Joseph Sachleben, Masis Isikbay, Hari Singhal, Geoffrey Greene, Donald Vander Griend, Suzanne Conzen, Mark J Ratain
There is limited knowledge regarding the metabolism of megestrol acetate (MA), as it was approved by FDA in 1971, prior to the availability of modern tools for identifying specific drug-metabolizing enzymes. We determined the cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs) that metabolize MA, identified oxidative metabolites, and determined pharmacologic activity at the progesterone, androgen and glucocorticoid receptors (PR, AR, and GR, respectively). Oxidative metabolites were produced using human liver microsomes (HLMs), and isolated for mass spectral (MS) and nuclear magnetic resonance (NMR) analyses...
October 20, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29050520/evaluation-of-the-pharmacokinetics-tissue-distribution-and-excretion-studies-of-ymr-65-a-tubulin-polymerization-inhibitor-with-potential-anticancer-activity-in-rats-using-uplc-ms-ms
#20
Ali Fan, Yaliang Zhang, Qing Zhang, Jiali Wei, Xiaoyu Lu, Guanghui Ren, Di Zhao, Ning Li, Hailiang Zhu, Xijing Chen
1. YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a new tubulin polymerization inhibitor with encouraging anticancer activity. 2. The validated ultra-performance liquid chromatography-tandem mass spectrometer method was successfully applied to the pharmacokinetics, tissue distribution and excretion study of YMR-65 after oral and intravenous administration. The area under concentration-time curve (AUC0-∞) for YMR-65 were 151.67±54.48 and 459.45±49...
October 20, 2017: 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"