氧氟沙星(Ofloxacin)在鲤鱼体内的药代动力学

应用 HPL C法测定了单次混饲口服氧氟沙星 (10 mg/ kg)后 ,鲤鱼体内不同时间的血浆药物浓度。利用 MCPKP药代动力学软件分析数据 ,其药代动力学特征符合一级吸收一室开放模型 ,动力学方程为 C=3.2 94 31(e- 0 .0 4 34 1 t-e- 1 .1 1 474 t )。主要药代动力学参数 :吸收半衰期 (T1 /2 ka) 0 .6 2 16 7h,半衰期 (T1 /2 k) 15 .96 4 0 5 h,最高血药浓度 (Cmax)2 .775 89mg/ L ,出现最高血药浓度时间 (TPP,血药浓度时间曲线下面积 (AUC) 72 .934mg/ L· h,血浆治疗浓度维持时间 TCP(ther) 5 .4 4 10 h。结果表明 ,氧氟沙星在鲤鱼体内吸收较迅速 ,达峰时间较短 ,血药峰浓度高 ,消除缓慢 ,保持有效杀菌浓度时间长 。

Development of ELISA and immunochromatographic assay for ofloxacin

Two rapid, sensitive and reliable immunoassay methods, namely competitive indirect enzyme-linked immunosorbent assay (CI-ELISA) and colloidal gold-based immunochromatographic assay (CGIA), were developed to detect ofloxacin (OFL). The linear range of the CI-ELISA was from 0.5 to 128 ng/mL with a limit of detection (LOD) of 0.35 ng/mL. Good recoveries were obtained in analyzing simulated swine urine samples. The CGIA could accurately estimate OFL at concentrations as low as 10 ng/mL in less than 10 min, and test results were read visually without any instrument.

Highly sensitive trivalent copper chelate-luminol chemiluminescence system for capillary electrophoresis chiral separation and determination of ofloxacin enantiomers in urine samples

A simple,fast and sensitive capillary electrophoresis（CE） strategy combined with chemiluminescence（CL） detection for analysis of ofloxacin（OF） enantiomers was established in the present work.Sulfonated p-cyclodextrin（β-CD） was used as the chiral additive being added into the running buffer of luminol-diperiodatocuprate（Ⅲ）（K[Cu（HIO6）2],DPC） chemiluminescence system.Under the optimum conditions,the proposed method was successfully applied to separation and analysis of OF enantiomers with the detection limits（S/N=3） of 8.0 nM and 7.0 nM for levofloxacin and dextrofloxacin,respectively.The linear ranges were both 0.010-100 μM.The method was utilized for analyzing OF in urine;the results obtained were satisfactory and recoveries were 89.5-110.8%,which demonstrated the reliability of this method.This approach can also be further extended to analyze different commercial OF medicines.

In vitro and in vivo evaluation of gastroretentive floating drug delivery system of ofloxacin

This study aimed to develop hydrophilicmatrix based controlled release gastroretentive drug delivery system of ofloxacin and conducting its in vitro and in vivo evaluations.Effervescent floating gastroretentive drug delivery system of ofloxacin was prepared utilizing Boxe Behnken statistical design with 3 factors,3 levels and 15 experimental trials.Formulation optimization was done by setting targets on selected responses.In vivo studies were carried out for the optimized formulation with 12 healthy human volunteers and obtained pharmacokinetic parameters were compared with themarketed once daily formulation,“Zanocin OD”.Optimized formulation showed satisfactory controlled in vitro drug release for more than 12 h with excellent buoyancy properties(floating lag time<1 min,floating duration>16 h).Optimized and marketed formulations were found to have similar in vitro release profile(f2¼79.22)and also were found to be bioequivalent.Serum ofloxacin concentration was well maintained above its reported minimum inhibitory concentrations for most of the pathogens for sufficiently longer duration.Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product despite their bioequivalence.Bettertherapeutic effect can be expected since ofloxacin exhibits concentration dependent killing.Hence,gastroretention can be a promising approach to enhance bioavailability of ofloxacin with narrow absorption window in upper GIT.

Synthesis and Characterization of Soy Protein Isolate/MMT Nanocomposite Film for the Control Release of the Drug Ofloxacin

Nanocomposites were prepared by blending soy protein isolate with different percentage of MMT by melt extrusion technique. The nanocomposites were characterized by using, XRD, TEM, SEM and TGA methods. The XRD studies indicated the absence of diffraction peaks for the bio-nanocomposites. From the TEM studies it was ascertained that the degree of exfoliation increased with increase in MMT content. The morphology of the nanocomposites was ascertained from the SEM studies. The degradation pattern of the nano-composites was evaluated from the TG analysis. The drug delivery system of the nanocmposites was investigated by blending the nanocomposites with ofloxacin at different pH media. The various kinetic parameters were evaluated and the mechanism of drug delivery has been postulated based on the kinetic data.

Taste masking of ofloxacin and formation of interpenetrating polymer network beads for sustained release

The objective of this study was to carry out taste masking of ofloxacin(Ofl) by ion exchange resins(IERs)followed by sustained release of Ofl by forming interpenetrating polymer network(IPN) beads. Drug-resin complexes(DRCs) with three different ratios of Ofl to IERs(1:1, 1:2, 1:4) were prepared by batch method and investigated for in vivo and in vitro taste masking. DRC of methacrylic acid-divinyl benzene(MD) resin and Ofl prepared at a ratio of 1:4 was used to form IPN beads. IPN beads of MD 1:4 were prepared by following the ionic cross-linking method using sodium carboxymethyl xanthan gum(SCMXG) and SCMXG-sodium carboxymethyl cellulose(SCMXG-SCMC). IPN beads were characterized with FT-IR and further studied on sustained release of Ofl at different pH. In vivo taste masking carried out by human volunteers showed that MD 1:4 significantly reduced the bitterness of Ofl. Characterization studies such as FT-IR, DSC, P-XRD and taste masking showed that complex formation took place between drug and resin. In vitro study at gastric pH showed complete release of drug from MD 1:4 within 30 min whereas IPN beads took 5 h at gastric pH and 10 h at salivary pH for the complete release of drug. As the crosslinking increased the release kinetics changed into non-Fickian diffusion to zero-order release mechanism. MD 1:4 showed better performance for the taste masking of Ofl and IPNs beads prepared from it were found useful for the sustained release of Ofl at both the pH, indicating a versatile drug delivery system.

PVA Nanofibers Containing Ofloxacin-Cyclodextrin Inclusion Complex: Improve Optical Stability of Ofloxacin

Ofloxacin is an antibiotic with a wide range of activity against bacterial infections, but due to the high potential for toxicity when exposed to light, resolving this problem and further stabilizing the drug are among the posed challenges. Inclusion complex formation between α-cyclodextrin (α-CD), ofloxacin (OFL) and polyethylene glycol (PEG) was prepared via two methods to produce nanocontainers with desirable stability. The effect of PEG as compatible solubilizing agent and mixing condition (in ultrasonic bath) were investigated in formation of an inclusion complex between α-CD/OFL. Obtained complexes were examined by FTIR, H-NMR, SEM, EDX and UV which indicated the formation of an inclusion complex between α-CD/OFL, in turn, is a mixture of the cage and channel structures. Differences between 1H-NMR, FTIR and XRD spectra of OFL, CDs and inclusion complex indicated the formation of α-CD/OFL and supramolecular containers in solid phase. These inclusion complexes loaded in PVA-based nanofibers for smart nanofibers with controlled release manner and higher stability of OFL. Obtained nanofiber showed that nanofibers containing CDs/OFL under sonic energy containing higher degree of OFL.

TNF /TNFR1 signaling pathway and endocytoplasmic reticulum stress (ERs) mediated apoptosis are involved in ofloxacin and marbofloxacin-induced apoptosis of juvenile dog joint chondrocytes in early stage in vitro.

Quinolones (QNs) are widely used for their broad antibacterial spectrum and good antibacterial activities,desirable pharmacokinetic characteristics and few cross reactions with other therapeutic agents. However,QNs have adverse effects including chondrotoxicity in juvenile animals,so the use of QNs is contraindicated in children and adolescents. In regarding to the chondrotoxicity of QNs,numerous studies have been done. The current hypothesis suggests that QNs compete with the β1 integrin receptors residing on chondrocyte surface for extracellular Mg ions,which leads to alternation in β1 integrin expression,or function and eventually results in chondrocyte death. Stupack et al (2001)demonstrated that caspase-8 could be recruited to unligated integrins in adherent cells and further initiate apoptosis in a death receptor-independent manner. Sheng et al (2008) found that ofloxacin induced rabbit's chondrocyte apoptosis by causing disturbance of β1 integrin functions and subsequently through caspase-8-dependent mitochondrial pathway.Apoptosis could be initiated through the stimulation of death receptors and through an intrinsic pathway from mitochondria. Santangelo and Bertone (2011) and Wu et al (2011) found that TNFα could be expressed in human primary condrocytes inducing by interleukin-1beta (IL-1) or lipopolysaccharide (LPS). However,to date there have not been sufficient results to support that signaling from the death receptors was involved in QNs-induced chondrocyte apoptosis.In addition,dilated cisternae of rough endoplasmic reticulum (ER) have been noticed in QNs-induced arthropathy.ER can participate in the initiation of apoptosis. Varieties of harmful cellular stimuli could lead to ERs (ER stress). Elevated ERs results in cellular apoptosis. But whether ERs mediates apoptosis in QNs-treated chondrocytes is not clear yet.In this study,we chose two QNs agents and chondrocytes were treated with ofloxacin and marbofloxacin at final concentrations of 20 μg / mL,50 μg / mL and 100 μg / mL respectively in vitro for 2 h,8 h and 24 h. Cell survival rate,cell apoptosis rate and death receptor pathway factors TNFα (intracellular tumor necrosis factor-alpha),TNFR1 (TNF receptor-1),TRADD (TNF receptor 1 associated via death domain),FADD (Fas-associated protein with death domain),caspase-8 and ERs mediated apoptosis factors caspase-12,GADD153 (CHOP or DDIT3),GRP78 (Bip),calpain,and anti-apoptosis factors Bcl-2 (B-cell lymphoma 2),NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) gene expression levels were measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) analysis to determine the dose-response relationship. We further silenced the expression of TNFR1 successfully by transferring TNFR1-siRNA to chondrocytes to confirm whether TNFα / TNFR1 signaling pathways are involved ofloxacin and marbofloxacin-induced apoptosis. Furthermore,expression of death receptor pathway representative proteins TNFα / TNFR1 and endocytoplasmic reticulum (ER) pathway representative protein caspase-12 were confirmed using Western Blot.We have found that ofloxacin and marbofloxacin could induce apoptosis of chondrocytes in a time-and dose-dependent fashion within 24 h. mRNA of TNFα,TNFR1,TRADD,FADD and caspase-8 (caspase-8 of ofloxacin treated group were at 24 h) were highly expressed at 8 h,and GADD153,GRP78,calpain and caspase-12 at 8 h or 24 h,and antiapoptosis factors NF-κB and Bcl-2 were also raised after 2 h,all in a dose-dependent fashion. Expression of caspase-8was downregulated after silenced TNFR1. TNFα and TNFR1 proteins were expressed at 8 h and caspase-12 proteins were expressed at 24 h. In addition,ofloxacin showed a higher toxicity.Our results indicate that death receptor pathway TNF / TNFR1 and ERs mediated apoptosis factors are involved in ofloxacin and marbofloxacin-induced apoptosis of in vitro cultured juvenile dog joint chondrocytes within 24 h.

Cuprous Oxide/Nitrogen-doped Graphene Nanocomposites as Electrochemical Sensors for Ofloxacin Determination

Cu2O/nitrogen-doped grapheme（NG） nanocomposite material was prepared via a facile one step chemical reduction and characterized by means of X-ray diffraction（XRD） and scanning electron microscopy（SEM）. A new electrochemical sensor was then fabricated by coating Cu2O/nitrogen-doped graphene nanocomposite with Nation on glassy carbon electrode（Cu2O/NG/Nation/GCE）. The electrochemical response of this modified electrode toward of- loxacin was examined by cyclic voltammetry. The results indicate that Cu2O/NG/Nafion composite-modified elec- trode exhibits higher catalytic activity in the electrochemical oxidation of ofloxacin compared with glassy carbon electrode（GCE）, Cu2O/Nafion modified electrode（Cu2O/Nafion/GCE）, and N-doped graphene/Nation modified electrode（NG/Nafion/GCE）. Under optimal conditions, the peak current was found to be linearly proportional to the concentration of ofloxacin in the 0.5-27.5 μmol/L and 27.5-280 μmol/L ranges with a lower detection limit of 0.34 μmol/L, higher sensitivity of 39.32 μA-L-mmoV1 and a shorter reaction time of less than 2 s. In addition, Nation can enhance the stability of the modified electrode and prevent some negative species. Thus the modified electrode exhibits good selectivity and a long working life. The Cu2O/NG/Nafion composite modified electrode shows promising application in electrochemical sensors, biosensors, and other related fields because of its excellent properties.

Degradation of ofloxacin using peroxymonosulfate activated by nitrogen-rich graphitized carbon microspheres:Structure and performance controllable study

Nitrogen-rich graphitized carbon microspheres(NGCs)with hierarchically porous were constructed by self-assembly.Under different heat treatment conditions,the structure,morphology and properties of NGCs were studied by using multiple characterization techniques.The results showed that the chemical microenvironments(e.g.surface chemistry,degree of graphitization and defective,etc.)and microstructures properties(e.g.morphology,specific surface area,particle size,etc.)could be delicately controlled via thermal carbonization processes.The degradation of ofloxacin(OFLX)by NGCs activated peroxymonosulfate(PMS)was studied systematically.It was found that the synergistic coupling effect between optimum N or O bonding species configuration ratio(graphitic N and C=O)and special microstructure was the main reason for the enhanced catalytic activity of NGC-800(calcination temperature at 800°C).Electron paramagnetic resonance(EPR)experiments and radical quenching experiments indicated that the hydroxyl(·OH),sulfate(SO4^·-)and singlet oxygen(^1O_(2))were contributors in the NGC-800/PMS systems.Further investigation of the durability of chemical structures and surface active sites revealed that undergo N bonding species configuration reconstruction and cannibalistic oxidation during PMS activation reaction.The used NGC-800 physicochemical properties could be recovered by heat treatment to achieve the ideal catalytic performance.The findings proposed a valuable insight for catalytic performance and controllable design of construction.

Racemic ofloxacin separation by supported-liquid membrane extraction with two organic phases

Based on chemical thermodynamic theory, racemic ofloxacin is separated in chiral sys-tems by hollow fiber liquid-supported membrane technology combining with countercurrently frac-tional extraction. The two chiral solutions containing L-dibenzoyltartaric acid and D-dibenzoylta- rtaric acid in 1-octanol, flow through the lumen side and the shell side of fibers, respectively. The solution which flows through the lumen side of fibers also contains racemic ofloxacin. The wall of hollow fibers is filled with an aqueous of 0.1 mol/L Na2HPO4/H3PO4 buffer solution of pH = 6.86 containing 2 mmol/L of cetyltrimethyl ammonium bromide for 48 h. The fairly polar ofloxacin can cross the membrane back and forth, but dibenzoyltartaric acids cannot cross it. Fractional chiral extraction theory, mass transfer performance of hollow fiber membrane and enantioselectivity are investigated. Mathematical model of R/S = 0.96e0.03NTU for racemic ofloxacin separation by hollow fiber extraction, is established. The optical purity for ofloxacin enantiomers is up to 90% when 11 hollow fiber membrane modules of 22 cm in length in series are used.

Sunlight photocatalytic degradation of ofloxacin using UiO-66/wood composite photocatalysts

This study synthesized UiO-66(Zr)in situ on wood via a one-step solvothermal method.UiO-66/wood was successfully prepared and its catalytic performance for the ofloxacin(OFX)photodegradation under simulate sunlight was also explored.UiO-66/wood exhibited a better catalytic performance,and its degradation rate constant was about 1.2 and 1.5 times than that of UiO-66 and wood,respectively.The effects of solution initial concentration,pH of the system and dosage of the photocatalyst were explored.Additionally,the active species trapping experiments and UV-vis diffused reflectance spectra measurements were conducted to investigated the photocatalytic mechanism of the UiO-66/wood composite,superoxide radical(O_(2)^(·-))and hydroxyl radical(^(·)OH)were the main reactive species.In addition,the possible degradation pathways of OFX were analyzed by LC-MS.Meanwhile,the UiO-66/wood showed outstanding stability and reusability after 4 cycles experiments.The removal performance of UiO-66/wood towards real samples showed it has potential in actual application.

Removal of ofloxacin antibiotic using heterogeneous Fenton process over modified alginate beads

The aim of this work is to study the heterogeneous oxidative degradation of ofloxacin antibiotic using a composite material prepared from sodium alginate and cyclohexane dinitrilo tetraacetic acid（CDTA）. The characterization tests indicated the successful incorporation of metal chelator and iron. It was also demonstrated that the synthesized beads are mesoporous. The influence of several experimental parameters（i.e.： H2O2 dose,working temperature, beads loading and initial drug concentration） on the process performances was evaluated. The reaction temperature significantly affects the drug conversion efficiency. It was also observed that the synthesized material was efficient toward the target antibiotic degradation in the presence of small quantities of hydrogen peroxide. Under optimum conditions（0.05 g of granules, initial drug concentration = 10 mg/L,25 μL of 10 mmol/L H2O2）, conducted in a batch reaction, 94% degradation of ofloxacin was reached. The results also indicate that the composite material showed a reasonable stability;a relatively low decrease of activity after four successive runs（only 9%） and a negligible iron leaching（0.8%） have been observed. The synthesized composite material offered interesting advantages in terms of simplicity, good stability, ease of recovery from the liquid medium after use and its efficiency in the presence of low quantities of oxidant. It constitutes a good candidate in the water treatment area.

Statistical modeling of radiolytic (6OCo γ) degradation of Ofloxacin, antibiotic: Synergetic effect, kinetic studies & assessment of its degraded metabolites

The impact of human activities in the past few decades has paved the way for the release of pollutants due to the improper effluent treatment. Recent studies revealed that, Ofloxacin, an antibiotic as one of the major pollutant affecting surface water and ground water. In this study, the radiolytic potential of Ofloxacin was investigated. The effects of pH, dose and concentration of Ofloxacin were analyzed using One Factor At a Time (OFAT) and the interactive effects between the parameters were studied using Face Centered Central Composite Design. The statistically optimised developed model shows 30% degradation at initial antibiotic concentration of ImM at pH 3.0 and at 2 kGy dose of gamma ray. The process efficiency was evaluated in terms of G value and its correlation with the concentration of antibiotic was also established. The process of degradation was augmented by the addition of H2O2 (1.5 mM). The reaction kinetics for the process was evaluated, the dose rate constant and the rate of degradation for the augmented process was found to be 0.232 kGy^-1 and 0.232 mM/kGy, respectively. The degraded metabolites of the radiolytic degradation of Ofloxacin were analyzed through change in pH, reduction in TOC and GC-MS spectrum.

Study on the susceptibility genes that mediate the resistance of Helicobacter pylori to clarithromycin and levofloxacin based on comprehensive antibiotic research database comparison

Objective To explore the new genes related to the resistance of H. pylori to clarithromycin (CLA) and levofloxacin (LVX) based on whole-genome sequencing.Methods From September 1st, 2016 to August 31st,2019, 1 749 patients with upper gastrointestinal symptoms and positive13C urea breath test who visited the Department of Gastroenterology and Hepatology, the University of Hong Kong-Shenzhen Hospital were enrolled.

Clinical Efficacy of ciprofloxacin and ofloxacin

The cliniueal efficacy, antibacterial activity and adverse effects of ciprofloxacin (CPLX) and ofloxacin (OFLX) produced in our country were compared in five clinical hospitals in Beijing and Guangzhou in 1992. Two groups, each consisting of 100 cases, were treated with. CPLX and OFLX respectively. The

Induction in vitro and stability of Mycobacterium tuberculosis resistance to ofloxacin

Objective To induct Mycobacterium tuberculosis(MTB)resistance with ofloxacin(Ofx)of stepwise increasing concentration in vitro,investigate stability to fluoroquinolone(FQs)antibiotic of MTB,and analyze the molecular mechanism and mutation specialty of drug resistance preliminarily.Methods MTB Standard

Degradation potential of ofloxacin and its resulting transformation products during Fenton oxidation process

The degradation of ofloxacin(OFX)in the aqueous solution by Fenton oxidation process was investigated in the present study.The optimum operating conditions for the degradation of OFX in our system was determined.More importantly,the degradation pathways on a basis of the identification of transformation products during the degradation of OFX were proposed,which revealed that the initial degradation step could be associated with the decarboxylation at the quinolone moiety.Moreover,the detachment of the F element during the Fenton oxidation process has also been detected.Since the carboxylic group within OFX has been considered as an important bridge for binding quinolones with the DNA gyrase target,the decarboxylation process would offer insights into the reduction of antibacterial potentials.