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pharmacokinetics, rat

Yilin Sun, Le Zhen, Ying Peng, Jiankun Wang, Fei Fei, Lixiang Aa, Wenjiao Jiang, Xue Pei, Li Lu, Jie Liu, Guangji Wang, Kun Hao
To improve bioavailability and provide resistance to deamination, an array of gemcitabine (dFdC) prodrugs carrying the acyl modifications has been successful in the optimization of pharmacokinetic properties of dFdC, but the reports about 4-N-carbobenzoxy-dFdC (Cbz-dFdC), a dFdC prodrug bearing alkyloxycarbonyl modification, are relatively rare. Notably, in vivo enzymatic hydrolysis was an absolutely essential factor for the activation of these prodrugs, which is correlated with the anti-tumor activity. Therefore, detailed metabolism studies of Cbz-dFdC should be carried out for a more authentic pharmacodynamic evaluation...
March 14, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Hitoshi Ono, Yasunari Kojima, Hiroshi Harada, Yoshikazu Abe, Takuro Endo, Mamoru Kobayashi
1. The pharmacokinetic and metabolite profiles of mizagliflozin, a novel selective sodium glucose co-transporter 1 inhibitor designed to act only in the intestine, were investigated in rats. 2. Mizagliflozin administrated intravenously (0.3 mg/kg) and orally (3 mg/kg) declined with a short half-life (0.23 and 1.14 h, respectively). The absolute bioavailability was only 0.02%. Following intravenous administration of [14 C]mizagliflozin (0.3 mg/kg), radioactivity in plasma was also rapidly declined. Up to 24 h after oral administration of [14 C]mizagliflozin (1 mg/kg), radioactivity was recovered in the faeces (98...
March 20, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Michał Romański, Jacek Wachowiak, Franciszek K Główka
Treosulfan is a prodrug that undergoes a highly pH- and temperature-dependent nonenzymatic conversion to the monoepoxide {(2S,3S)-1,2-epoxy-3,4-butanediol 4-methanesulfonate [S,S-EBDM]} and diepoxide {(2S,3S)-1,2:3,4-diepoxybutane [S,S-DEB]}. Currently, treosulfan is tested in clinical trials as an alternative to busulfan in conditioning prior to hematopoietic stem cell transplantation (HSCT). Of note, the optimal dosing of the prodrug is still unresolved, especially in infants. In this paper, the pharmacokinetics of treosulfan, together with its biologically active epoxides, is comprehensively reviewed for the first time, with the focus on conditioning prior to HSCT...
March 19, 2018: Clinical Pharmacokinetics
Yeong Ran Jeong, Rae Ung Jeong, Jeong Hyun Son, Joon Cheol Kwon, Saem Jung, Mi A Song, Jin Ah Hwang, Gyun Min Lee
BACKGROUND: For regulatory approval, the comparability of a biosimilar product to an originator product should be ensured through thorough physicochemical and biological characterization. OBJECTIVE: To evaluate the biosimilarity between LBDE, the proposed biosimilar darbepoetin alfa, and NESP® , its originator, we performed a comprehensive physicochemical and biological characterization study. METHODS: Primary and higher-order protein structures were analyzed using Lys-C peptide mapping with liquid chromatography-mass spectrometry (LC-MS), disulfide bond identification, circular dichroism, and fluorescence spectroscopy...
March 19, 2018: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Xiabin Chen, Jing Deng, Wenpeng Cui, Shurong Hou, Jinling Zhang, Xirong Zheng, Xin Ding, Huimei Wei, Ziyuan Zhou, Kyungbo Kim, Chang-Guo Zhan, Fang Zheng
Cocaine abuse is a worldwide public health and social problem without a US Food and Drug Administration (FDA)-approved medication. Accelerating cocaine metabolism that produces biologically inactive metabolites by administration of an efficient cocaine hydrolase (CocH) has been recognized as a promising strategy for cocaine abuse treatment. However, the therapeutic effects of CocH are limited by its short biological half-life (e.g., 8 h or shorter in rats). In this study, we designed and prepared a set of Fc-fusion proteins constructed by fusing Fc(M3) with CocH3 at the N-terminus of CocH3...
March 19, 2018: AAPS Journal
Haoshi Gao, Yue Wei, Long Xi, Yuanyuan Sun, Tianhong Zhang
Bergenin (BN) is a Biopharmaceutics Classification System class IV (BCS IV) drug with poor hydrophilicity and lipophilicity and is potentially eliminated by the efflux function of P-glycoprotein (P-gp). These factors may explain its low oral bioavailability. In the present study, a BN-phospholipid complex solid dispersion (BNPC-SD) was prepared by solvent evaporation and characterized based on differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, infrared diffraction, solubility, octanol-water partition coefficient, and in vitro dissolution...
March 19, 2018: AAPS PharmSciTech
Kavitha Ranganathan, Eric Simon, Jeremy Lynn, Alicia Snider, Yu Zhang, Noah Nelson, Alexis Donneys, Jose Rodriguez, Lauren Buchman, Dawn Reyna, Elke Lipka, Steven R Buchman
PURPOSE: Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. METHODS: Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite)...
March 19, 2018: Pharmaceutical Research
Xianhua Zhang, Linran Han, Jin Liu, Qiuyue Xu, Yuxin Guo, Wan Zheng, Jian Wang, Xi Huang, Ping Ren
In the present study, the pharmacokinetics of multi-components (naringenin, nobiletin, meranzin hydrate, narirutin, naringin, hesperidin, and neohesperidin) were investigated in acute depressive rats following oral administration of Fructus Aurantii (Zhi-Qiao, ZQ) extract (20 g/kg). A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to quantitatively or qualitatively analyze the 7 absorbed ingredients in the plasma, hippocampus and cortex of acute depressive rats...
2018: Frontiers in Pharmacology
Ken-Ichi Kaneko, Masaaki Tanaka, Akira Ishii, Yumiko Katayama, Takayoshi Nakaoka, Satsuki Irie, Hideki Kawahata, Takashi Yamanaga, Yasuhiro Wada, Takeshi Miyake, Kota Toshimoto, Kazuya Maeda, Yilong Cui, Masaru Enomoto, Etsushi Kawamura, Norifumi Kawada, Joji Kawabe, Susumu Shiomi, Hiroyuki Kusuhara, Yuichi Sugiyama, Yasuyoshi Watanabe
Various positron emission tomography (PET) probes have been developed to assess the in vivo activities of drug transporters in humans, that aid in the prediction of pharmacokinetic properties of drugs and the impact of drug-drug interactions. We developed a new PET probe, [11C ]dehydropravastatin ([11 C]DPV), and demonstrated its usefulness for the quantitative investigation of Oatps/SLCO and Mrp2/ABCC2 in rats. To further analyze the species differences and verify the pharmacokinetic parameters in humans, serial PET scanning of the abdominal region with [11 C]DPV was performed in six healthy volunteers with and without an OATP1Bs and MRP2 inhibitor, rifampicin (600 mg, oral), in a crossover fashion...
March 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Margrit M Ayoub, Neveen G Elantouny, Hanan M El-Nahas, Fakhr El-Din S Ghazy
For patient convenience, sustained release Adefovir Poly-d,l-lactic-co-glycolic acid (PLGA) microspheres were formulated to relieve the daily use of the drug which is a problem for patients treated from chronic hepatitis-B. PLGA microspheres were prepared and characterized by entrapment efficiency, particle size distribution and scanning electron microscopy (SEM). In-vitro release and in-vivo studies were carried out. Factors such as drug: polymer ratio, polymer viscosity and polymer lactide content were found to be important variables for the preparation of PLGA Adefovir microspheres...
March 16, 2018: European Journal of Pharmaceutical Sciences
Yu-Tian Zhang, Mei-Feng Xiao, Qiong Liao, Wen-Long Liu, Kai-Wen Deng, Yi-Qun Zhou, Yu Tang, Fu-Yuan He, Yan-Tao Yang
BACKGROUND: It is well-known that the public still have been facing on a severe issue about the inconsistency of quality and therapeutic efficacy of traditional medicines. Recently, Professor Chang-Xiao Liu has created a new promising concept for identifying relevant quality-markers (Q-marker) from herbs, their formulas and manufacturing products. Therefore, building up a new approach is necessary for us to bridge over quality to efficacy of pharmaceutical products. STUDY DESIGN: In this paper, five candidate Q-markers, astragaloside IV, paeonflorin, amygdalin, tetramethylpyrazine, ferulic acid in Buyanghuanwu injection (BYHWI) had been designed to carry out in rat by using single and polypharmacokinetic models for total quanta to ascertain adequate Q-marker...
March 7, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Mahendra Shukla, Femi M Francis, Jawahar Lal
Conessine, a steroidal alkaloid obtained from the bark and seeds of the plant species of Apocynaceae family, elicits a histamine antagonistic action, selectively for the H3 histaminergic receptors. This alkaloid is used mainly for the treatment of dysentery and helminthic disorders. For the quantification of conessine in serum, a liquid chromatography-tandem mass spectrometry method was developed. Chromatographic separation was achieved on a Zorbax SB-CN column (100 × 4.6 mm, 3.5 µm), and a mobile phase consisting of 90% methanol in aqueous ammonium acetate buffer (pH 3...
January 1, 2018: European Journal of Mass Spectrometry
Yi Zhou, Qingqing Chang, Wenjie Wang, Xiaofang Zhang, Fang Zhou, Jianguo Sun, Guangji Wang, Ying Peng
FY363 is a new chemical entity of gemcitabine analog, which has been shown to have a significant inhibitory effect on cell proliferation in a variety of tumor cell lines in vitro. As a carbamate derivative, FY363 would be converted to the active metabolite gemcitabine through enzyme action in vivo. In order to clarify the exposure of FY363 prototype and its metabolite gemcitabine in vivo after administration of FY363, a sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and validated to simultaneously determine FY363 and gemcitabine in rat plasma after liquid-liquid extraction with ethyl acetate...
March 14, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Xie-An Yu, John Teye Azietaku, Jin Li, Hui Wang, Fang Zheng, Jia Hao, Yan-Xu Chang
Ardisia japonica is a well-known traditional Chinese medicinal herb used as a diuretic, for treating cough and for stopping uterine bleeding. A simple, sensitive, and reliable LC-MS/MS method was developed to determine six active compounds in rat plasma and this method was further applied to the pharmacokinetic study of these compounds after oral administration of Ardisia japonica extract. Acetonitrile was used to precipitate the protein in the plasma samples. Using acetonitrile and formic acid aqueous solution (0...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Jhohann Richard de Lima Benzi, Priscila Akemi Yamamoto, Jessica Hanna Stevens, Amanda Martins Baviera, Natália Valadares de Moraes
PURPOSE: We investigated the influence of diabetes mellitus (DM), glycemic control with insulin, cimetidine (Oct2 inhibitor) and metformin (Oct2 substrate) on the kinetic disposition of GAB in rats. MAIN METHODS: Male Wistar rats were divided in five groups and all animals received an oral dose of 50 mg/kg GAB: (vehicle + GAB), cimetidine + GAB (single dose of cimetidine [100 mg/kg] intraperitoneally 1 h before GAB), metformin + GAB (single dose of metformin 100 mg/kg by gavage concomitantly with GAB), DM + GAB (single dose of 40 mg/kg streptozotocin (STZ) intravenously) and DM + GAB + insulin (single dose 40 mg/kg STZ intravenously and 2 IU insulin twice daily for 15 days)...
March 15, 2018: Life Sciences
Hélène Chapy, Leonid Kagan
With a long half-life, pharmacokinetic evaluation of monoclonal antibodies in rodents lasts multiple weeks during which the animals may grow significantly. We evaluated the impact of weight, age and previous drug exposure on the pharmacokinetics of rituximab. Serum concentrations of rituximab were measured after intravenous and subcutaneous dosing, in Sprague-Dawley rats between 7 to 21 weeks old and weighing between 200 to 600 g. The growth of rats during the study was incorporated into the model through the increase of the volumes of compartments in relation to the rats total body weight...
March 15, 2018: Journal of Pharmaceutical Sciences
Rikard Pehrson, Tove Hegelund-Myrback, Danen Cunoosamy, Sara Asimus, Paul Jansson, Naimish Patel, Annika Borde, Sofia Lundin
Inhaled drugs generally aim to drive a local pharmacological effect in the lung while minimizing systemic exposure, in order to obtain efficacy in lung disease without unwanted systemic effects. Here, we demonstrate that inhaled delivery of a p38 inhibitor (AZD7624) can provide superior pharmacokinetic exposure and superior pharmacodynamic lung effects. In rats, inhaled AZD7624 had a 5 times higher dose-adjusted lung exposure compared to intravenous dosing. In healthy volunteers, LPS-induced TNFα in sputum has been shown to be significantly reduced (85%) by means of inhaled AZD7624...
March 16, 2018: Journal of Pharmacology and Experimental Therapeutics
Wei Li, Navaneethakrishnan Polachi, Xiangyang Wang, Yang Chu, Yuan Wang, Meng Tian, Dekun Li, Dazheng Zhou, Shuiping Zhou, Aichun Ju, Yubo Li, Yanjun Zhang, Min Chen, Luqi Huang, Changxiao Liu
BACKGROUND: The quality of Chinese medicine (CM) has being an active and challenging research area for CM. Prof. Chang-Xiao Liu et al first proposed the concept of quality marker (Q-Marker) for the quality evaluation and control on CM. This article describe the exploratory studies of Q-Marker in salvianolic acids for injection (SAI) based on this new concept. PURPOSE: This study was designed to screen Q-Marker of SAI and establish its quality control method based on the concept of CM Q-Marker...
February 10, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Wenge Chen, Yunlong Cheng, Jianzhong Chen, Jiahang Chen, Kai Jiang, Yuyang Zhou, Lee Jia
Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes...
March 8, 2018: Journal of Pharmaceutical and Biomedical Analysis
Xiaobo Wang, Yinan Wang, Ronggang Xi, Yuanyuan Wang, Xiaobo Yang
The optimization of process parameters of spray-dried powder containing fanhuncaoin, a newly discovered antiinflammatorily active phenolic acid isolated from Chinese herb, was conducted using response surface methodology (RSM). The experimental results were fitted into partial cubic polynomial model to describe and predict the response quality in terms of the final angle of repose, aerodynamic diameter, respirable fraction (RF) and yield. The recommended optimum spray-drying parameters for development of fanhuncaoin powder with optimum quality were 110 °C inlet temperature, 0...
March 15, 2018: Drug Development and Industrial Pharmacy
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