Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

LiQin Zhu,JianWei Yang,Yuan Zhang,YongMing Wang,JianLei Zhang,YuanYuan Zhao,WeiLin Dong 대한약리학회 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intraabdominalinfected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profilesin various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections,induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Bloodplasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK modelwas developed in rats and extrapolated to human using GastroPlus software. The predictions wereassessed by comparing predictions and observations. In the plasma concentration versus time profileof moxifloxcinin rats, Cmax was 11.151 μg/mL at 5 min after the intravenous injection and t1/2 was2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart,liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue toplasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrationswere known, extrapolation of a PBPK model was a method to predict drug pharmacokineticsand penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well asother tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacindue to its high concentration distribution. This pathological model extrapolation may provide referenceto the PK/PD study of antibacterial agents.

Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

Zhu, LiQin,Yang, JianWei,Zhang, Yuan,Wang, YongMing,Zhang, JianLei,Zhao, YuanYuan,Dong, WeiLin The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.2

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

Effects of 1-MCP on Reactive Oxygen Species, Polyphenol Oxidase Activity, and Cellular Ultra-structure of Core Tissue in ‘Yali’ Pear (Pyrus bretschneideri Rehd.) during Storage

Yu Dong,Liqin Liu,Zhe Zhao,Huanhuan Zhi,Junfeng Guan 한국원예학회 2015 Horticulture, Environment, and Biotechnology Vol.56 No.2

1-methylcyclopropene (1-MCP) has been shown to delay fruit ripening and senescence during storage. In this study, we investigated the effects of 1.0 μL·L-1 1-MCP on the biochemical changes and cellular ultra-structure of the core tissue in ‘Yali’ pear (Pyrus bretschneideri Rehd.) fruits stored at 25 ± 2°C. Our results showed that 1-MCP treatment significantly decreased the rates of respiration and ethylene production before their climacteric peaks, inhibited the development of core browning, lowered the chlorogenic acid content and polyphenol oxidase activity before the onset of core browning, and preserved high levels of superoxide dismutase activity, ascorbic acid, and glutathione contents. Furthermore, it suppressed the accumulation of hydrogen peroxide, superoxide anion, and malondialdehyde in the core tissue, maintained the integral structure of the cell membrane and organelle, and delayed the accumulation of electron-opaque matters in the vacuoles of core cells. These results suggested that 1-MCP treatment could reduce the injury caused by reactive oxygen, inhibit the oxidation of phenolics, and keep the cell membrane intact in core cells, thus, delaying the core browning in ‘Yali’ pear during storage.

Micro Galvanic Cell To Generate PtO and Extend the Triple-Phase Boundary during Self-Assembly of Pt/C and Nafion for Catalyst Layers of PEMFC

Long, Zhi,Gao, Liqin,Li, Yankai,Kang, Baotao,Lee, Jin Yong,Ge, Junjie,Liu, Changpeng,Ma, Shuhua,Jin, Zhao,Ai, Hongqi American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.44

<P>The self-assembly powder (SAP) with varying Nafion content was synthesized and characterized by XRD, XPS, HRTEM, and mapping. It is observed that the oxygen from oxygen functional groups transfers to the surface of Pt and generate PtO during the process of self-assembly with the mechanism of micro galvanic cell, where Pt, carbon black, and Nafion act as the anode, cathode and electrolyte, respectively. The appearance of PtO on the surface of Pt leads to a turnover of Nafion structure, and therefore more hydrophilic sulfonic groups directly contact with Pt, and thus the triple-phase boundary (TPB) has been expanded.</P>

Composite varistors based on epoxy resin/La_0.8Sr_0.2MnO₃

Yang, Xinsheng,Kim, Hern,Yang, Liqin,Cheng, Cuihua,Zhao, Yong SAGE Publications 2014 Journal of composite materials Vol.48 No.6

<P>Polymer/perovskite manganese oxide (epoxy resin/La<SUB>0.8</SUB>Sr<SUB>0.2</SUB>MnO<SUB>3</SUB>) composites are prepared using bonded method. There is no reaction between La<SUB>0.8</SUB>Sr<SUB>0.2</SUB>MnO<SUB>3</SUB> and the polymer. The nonlinear current–voltage property is significantly affected by the content of polymer. The resistivity and nonlinear coefficient increase with the increase of polymer content. The resistivity of the composites is 5–9 orders of magnitude higher than that of the sintering ceramics. The nonlinear electrical behavior is an intrinsic property. Compared with conventional sintered ceramic varistors, the polymer/manganese oxide composite varistors have greater nonlinear coefficient above 45.</P>

Feasibility Study of Radiation Dose Reduction in Adult Female Pelvic CT Scan with Low Tube-Voltage and Adaptive Statistical Iterative Reconstruction

Xinlian Wang,Wen He,Jianghong Chen,Zhihai Hu,Liqin Zhao 대한영상의학회 2015 Korean Journal of Radiology Vol.16 No.5

To evaluate image quality of female pelvic computed tomography (CT) scans reconstructed with the adaptive statistical iterative reconstruction (ASIR) technique combined with low tube-voltage and to explore the feasibility of its clinical application. Ninety-four patients were divided into two groups. The study group used 100 kVp, and images were reconstructed with 30%, 50%, 70%, and 90% ASIR. The control group used 120 kVp, and images were reconstructed with 30% ASIR. The noise index was 15 for the study group and 11 for the control group. The CT values and noise levels of different tissues were measured. The contrast to noise ratio (CNR) was calculated. A subjective evaluation was carried out by two experienced radiologists. The CT dose index volume (CTDIvol) was recorded. A 44.7% reduction in CTDIvol was observed in the study group (8.18 ± 3.58 mGy) compared with that in the control group (14.78 ± 6.15 mGy). No significant differences were observed in the tissue noise levels and CNR values between the 70% ASIR group and the control group (p = 0.068–1.000). The subjective scores indicated that visibility of small structures, diagnostic confidence, and the overall image quality score in the 70% ASIR group was the best, and were similar to those in the control group (1.87 vs. 1.79, 1.26 vs. 1.28, and 4.53 vs. 4.57; p = 0.122–0.585). No significant difference in diagnostic accuracy was detected between the study group and the control group (42/47 vs. 43/47, p = 1.000). Low tube-voltage combined with automatic tube current modulation and 70% ASIR allowed the low CT radiation dose to be reduced by 44.7% without losing image quality on female pelvic scan.