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Alcohol consumption promotes arsenic absorption but reduces tissue arsenic accumulation in mice

Eco-Environment & Health 2023年第3期2卷 107-116页

作者： Hongyu Wang Albert L.Juhasz Yaosheng Zhang Lizhu Zhang Lena Q.Ma Dongmei Zhou Hongbo Li State Key Laboratory of Pollution Control and Resource Reuse Jiangsu Key Laboratory of Vehicle Emissions ControlSchool of the EnvironmentNanjing UniversityNanjing 210023China Future Industries Institute University of South AustraliaMawson LakesSouth Australia 5095Australia Department of Nanxin Pharm Nanjing 210000China Institute of Soil and Water Resources and Environmental Science College of Environmental and Resource SciencesZhejiang UniversityHangzhou 310058China

Alcohol consumption alters gut microflora and damages intestinal tight junction barriers,which may affect arsenic(As)oral *** this study,mice were exposed to arsenate in the diet(6μg/g)over a 3-week period and gavaged daily with Chinese liquor(0.05 or 0.10 mL per mouse per day).Following ingestion,78.0%and 72.9%of the total As intake was absorbed and excreted via urine when co-exposed with liquor at daily doses of 0.05 or 0.10 mL,significantly greater than when As was supplied alone(44.7%).Alcohol co-exposure significantly altered gut microbiota but did not significantly alter As biotransformation in the intestinal tract or *** lower relative mRNA expression was observed for genes encoding for tight junctions in the ileum of liquor co-exposed mice,contributing to greater As bioavailability attributable to enhanced As absorption via the intestinal paracellular ***,As concentration in the liver,kidney,and intestinal tissue of liquortreated mice was decreased by 24.4%-42.6%,27.5%-38.1%,and 28.1%-48.9%compared to control *** was likely due to greater renal glomerular filtration rate induced by alcohol,as suggested by significantly lower expression of genes encoding for renal tight *** addition,in mice gavaged daily with 0.05 mL liquor,the serum antidiuretic hormone level was significantly lower than control mice(2.83±0.59 vs.5.40±1.10 pg/mL),suggesting the diuretic function of alcohol consumption,which may facilitate As elimination via *** results highlight that alcohol consumption has a significant impact on the bioavailability and accumulation of As.

关键词： Arsenic speciation Alcohol consumption oral bioavailability Tissue accumulation Tight junctions

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bioavailability Improvement of SLMs Based Erythromycin Ethyl Succinate using Stearic Acid-Myrj-52-based SLM＇s

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Journal of Chemistry and Chemical Engineering 2017年第1期11卷 37-44页

作者： Uduma Eke Osonwa Stephen Olaribigbe Majekodunmi Emmanuella OnyechiN Harrison Thaddeus Gugu Department of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmaceutical Sciences Nnamdi Azikiwe UniversityAwka Anambra State Nigeria Department of Pharmaceutics and Pharmaceutical Technology Faculty of Pharmacy University of Uyo P.M.B 1017 UyoNigeria Department of Pharmaceutics and Pharmaceutical Microbiology and biotechnology Faculty of Pharmaceutical SciencesNnamdiAzikiwe University Awka Anambra State Nigeria

Solid lipid microparticles of erythromycin ethyl succinate were prepared using solvent evaporation method to improve its bioavailability and efficacy. The solvent was allowed to evaporate after which the various entrapments were determined; the best entrapment was used in the in vivo studies to determine the bioavailability and efficacy. This study was done with albino mice. The best entrapment obtained was 83% with a loading capacity of 2.9% （Batch D） and was used in comparison with the unformulated drug to check for the in vivo efficacy. The results show higher efficacy with the formulated drug than with the pure drug both in vitro and in vivo. The in vitro test results were better despite that some enzymes which need to act on the solid lipid microparticles were not present in the in vitro assay and could lead to a reduction in the release of the drugs. In conclusion, there was improvement in efficacy, and hence bioavailability.

关键词： Erythromycin ethyl succinate solidlipid microparticles oral bioavailability improved activity.

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Pharmacokinetics/Pharmacodynamics study of Fixtral SB as compared to supra bioavailable itraconazole and conventional itraconazole

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World Journal of Pharmacology 2023年第1期12卷 1-11页

作者： Syed Mujtaba Hussain Naqvi Monil Yogesh Neena Gala Snehal Muchhala Anand Arumugam Dhananjay Panigrahi Dipak Patil Rahul Rathod Amey Mane Medical Affairs Dr Reddy’s LaboratoriesHyderabad 500016India Global Clinical Management Dr Reddy’s LaboratoriesHyderabad 500016India Formulation Development Dr Reddy’s LaboratoriesHyderabad 500016India

BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic *** absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal *** To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 *** study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product *** pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product ***(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 *** events(AEs)assessments were performed in each study period and post-study *** Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),*** parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and *** severe AE was reported.

关键词： Supra-Bioavailable itraconazole Conventional itraconazole oral bioavailability Pharmacodynamics Efficacy Adverse events

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Nanosuspensions of Poorly Water Soluble Drugs Prepared by Precipitation-Combined Homogenization Technology based on Acid-Base Neutralization Reactions

Nanosuspensions of Poorly Water Soluble Drugs Prepared by Pr...

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2015年中国药学大会暨第十五届中国药师周

作者： Gang Shen Ling Cheng Lihong Zhang Baode shen Juanjuan Li Juan Zhen Rong Xu Hailong Yuan Pharmacy College Chengdu University of Traditional Chinese Medicine Department of Pharmacy Air Force General Hospital of PLA

Herpetospermum caudigerum lignans（HTL）, one of the potential drugs with the treatment of anti-hepatitis B virus and hepatoprotective effects, have been limited in clinical applications because of poor saturation solubility, resulting in low bioavailability. Both herpetrione（HPE） and herpetin（HPN） are considered as the most abundant ingredient in HTL and exhibit weak acidity. The purpose of this study was to produce dried preparations of HTL（composed of HPE and HPN） nosuspensions with high redispersibility using lyophilization. The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions, and variously critical formulation and process parameters affecting the characteristics of HTL-NS were optimized. The resultant products were characterized by particle size analysis, SEM, XRD, physical stability, solubility, dissolution and bioavailability. The dried preparations with a mean redispersed particle size of 286 nm was produced by using 4%（w/v） mannitol as cryoprotectants and possessed good physical stability at 4 oC or 25 oC for two months. Meanwhile, in vitro evaluation showed dried preparations could significantly increase saturation solubility and dissolution rate along with improving in vivo oral bioavailability, when compared with raw drug. This study provides a feasible drug delivery system for poorly water-soluble ingredients with pH-dependent solubility.

关键词： Herpetospermum caudigerum lignans nanosuspensions acid–base neutralization saturation solubility dissolution oral bioavailability

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Design and Synthesis of Chrysin Carboxylic Acid Derivatives

Design and Synthesis of Chrysin Carboxylic Acid Derivatives

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中国化学会第十七届全国有机分析与生物分析学术研讨会

作者： CAI cheng ZHANG Zhen-ning CHANG Peng-fei JIANG Bingli School of Chemistry and Chemical Engineering Guangxi University

＜正＞Chrysin（5,7-dihydroxyflavone）,a natural,widely distributed isoflavone,has diversebioactivities,including antioxidative[1,2],anticancer[3],anxiolytic[4],anti-inflammatory[5,6],anti-diabetic[7],and antiglucosidase characteristics[8].But the oral bioavailability of chrysinwas not in sufficient quantities to produce any biological *** our work,carboxylic wasintroduced to the chrysin by Friedel-Crafts acylation reaction for improving the oralbioavailability of chrysin.

关键词： Chrysin Friedel-Crafts acylation oral bioavailability

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Solid self-emulsifying pellets to improve oral absorption of poorly water soluble drugs:preparation and in vitro and in vivo evaluation

Solid self-emulsifying pellets to improve oral absorption of...

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2009年中国药学大会暨第九届中国药师周

作者： Yongjun Wang, Jin Sun, Xiaohong Liu, Yinghua Sun, Zhonggui He* (Department of pharmaceutics, College of pharmacy, Shenyang pharmaceutical university, Shenyang Liaoning Province 110016)

The oral delivery of poorly water soluble drugs presents a significant challenge to pharmaceutical scientists because of their low solubility in water, which leads to poor oral bioavailability, high intra- and inter-subject variability and lack of dose proportionality. Thus, for such drugs of biopharmaceutical class II （low solubility and high permeability）, the absorption rate and degree from the gastrointestinal tract （GIT） are controlled and limited by dissolution process. In recent years, self-emulsifying drug delivery systems （SEDDS） are recognized as a feasible approach to improve the dissolution and bioavailability of poorly soluble drugs. However, conventional SEDDS, which are mostly prepared in a liquid form and orally administered in soft or hard gelatin capsules, can make some disadvantages such as high production costs, low drug incompatibility and stability, drugs leakage and precipitation, capsule ageing. Then incorporation of liquid SEDDS into a solid dosage form is compelling and desirable. Recently, a new drug delivery technology-solid SEDDS （S-SEDDS） which combine the advantages of SEDDS and those of solid dosage forms, have been investigated. As a multiple-unit dosage form, pellets have some desired advantages, such as flexibility in designing and developing solid dosage form, reduction of intra- and inter-subject variability of drug dissolution and plasma profiles, hence improvement of the drug safety and efficacy. To prepare pellets, extrusion/ spheronization technique has become popular in pharmaceutical industry because it is easily large-scale, and its products have many features, including spherical shape, narrow modal size distribution, good flow properties, low friability and uniform packing characteristics.

关键词： Solid self-emulsifying drug delivery systems Pellets Extrusion/ spheronization Nitrendipine oral bioavailability

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