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1.
Braz. J. Pharm. Sci. (Online) ; 58: e18524, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364432

ABSTRACT

Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali


Subject(s)
Animals , Male , Female , Mice , Stomach/drug effects , Stomach Ulcer/pathology , Tissues/drug effects , Tissue Distribution , Astragalus Plant/adverse effects , Plants, Medicinal , Administration, Oral
2.
Article in Chinese | WPRIM | ID: wpr-879026

ABSTRACT

The concentrations of seven anti-inflammatory components in blood and tissues were determined by UPLC-MS/MS after oral administration of Tetrastigma hemsleyanum aerial part(THAA) in healthy and inflammatory pathological model rats. The determination was carried out by using positive and negative ion switching technique, and multiple reaction monitoring(MRM) mode. The tissue distributions of the seven components in different physiological states were compared, and the patterns and characteristics of the effective components of THAA were studied. The results revealed that the seven effective components have large drug-time-curve areas(AUC) in heart, brain, small intestine, and stomach in both normal rats and inflammatory pathological model rats. This suggests that the anti-inflammatory effective component groups in THAA extract can all penetrate the blood-brain barrier, and have a large distribution area in gastrointestinal tract. It is inferred that gastrointestinal reabsorption may be one of the causes of the bimodal distribution of the drug-time curve of the drug blood distribution graph. As compared to normal rats, the effective component groups in THAA extract have higher drug-time curve area(AUC) in heart, brain, small intestine, stomach, liver, spleen, lung, kidney, and muscle of inflammatory pathological model rats. Among them, the effective component groups have the largest distribution area in heart, brain, small intestine, and stomach. This suggests that the binding force of organ tissues and drugs in the body may change under pathological conditions. It is speculated that the heart, brain, small intestine, and stomach may be the target tissues of THAA to produce anti-inflammatory effect. The retention times of THAA effective component groups in various organ tissues of rats in different physiological states are all relatively short, and do not have much difference. This suggests that no effective component accumulates in body, and that the pathological state of inflammation does not affect the onset times of the effective component groups. This experiment elucidates the patterns and characteristics of the in vivo target-effecting tissue distribution of THAA anti-inflammatory extract, and provides an experimental basis for clinical treatment.


Subject(s)
Animals , Anti-Inflammatory Agents , Chromatography, Liquid , Plant Components, Aerial , Plant Extracts , Rats , Tandem Mass Spectrometry , Tissue Distribution
3.
Rev. bras. ter. intensiva ; 32(2): 277-283, Apr.-June 2020. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1138494

ABSTRACT

RESUMO Objetivo: Determinar os níveis plasmáticos e o comportamento farmacocinético da micafungina em pacientes tratados com oxigenação por membrana extracorpórea. Métodos: As amostras foram colhidas por meio de pontos de acesso antes e depois da membrana, em dois hospitais espanhóis de nível terciário. Os momentos para o cálculo das curvas farmacocinéticas foram antes da administração do fármaco, e 1, 3, 5, 8, 18 e 24 horas após o início da infusão nos dias 1 e 4 de tratamento. Calcularam-se a área sob a curva, a depuração do fármaco, o volume de distribuição e a meia-vida plasmática por meio de análise farmacocinética não compartimental. Resultados: Os valores farmacocinéticos analisados no primeiro e quarto dias de tratamento não mostram qualquer diferença de concentração entre amostras colhidas antes da membrana e após a membrana, e o comportamento farmacocinético foi similar na vigência de diferentes falências de órgãos. A área sob a curva antes da membrana no dia 1 foi de 62,1 (IC95% 52,8 - 73,4) e a área sob a curva após a membrana nesse mesmo dia foi de 63,4 (IC95% 52,4 - 76,7), com p = 0,625. A área sob a curva antes da membrana no dia 4 foi de 102,4 (IC95% 84,7 - 142,8), enquanto a área sob a curva após a membrana nesse mesmo dia foi de 100,9 (IC95% 78,2 - 138,8), com p = 0,843. Conclusão: Os parâmetros farmacocinéticos da micafungina não foram alterados significantemente.


ABSTRACT Objective: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. Methods: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. Results: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. Conclusion: The pharmacokinetic parameters of micafungin were not significantly altered.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Extracorporeal Membrane Oxygenation , Micafungin/pharmacokinetics , Antifungal Agents/pharmacokinetics , Tissue Distribution , Prospective Studies , Area Under Curve , Tertiary Care Centers , Micafungin/administration & dosage , Half-Life , Antifungal Agents/administration & dosage
4.
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s45-s54, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057110

ABSTRACT

SUMMARY INTRODUCTION: Acute kidney injury (AKI) is highly prevalent today. It has a multifactorial aetiology and affects people of all ages, genders and ethnicities. Its treatment is essentially supportive of renal function substitution, so new treatment alternatives such as mesenchymal stem cell therapy (MSCs) should be investigated. METHODS: This review encompasses our understanding of the main mechanisms of action of MSCs in preclinical models of AKI by renal pedicle clamping ischemia-reperfusion, chemotherapy (cisplatin) and kidney transplantation in small and large animals, as well as outcomes in patients with AKI due to ischemia and kidney transplantation. RESULTS: Cellular therapy with MSCs has benefits in preclinical studies of AKI through various mechanisms, such as anti-inflammatory, antiapoptotic, oxidative anti-stress, antifibrotic, immunomodulatory and proangiogenic. In humans, MSC therapy is safe and effective. However, the challenges of MSC cell therapy include investigating protocols about the optimal dose of these cells, the route and frequency of appropriate administration, and the design of further biodistribution studies over a long follow-up period. In addition, a better understanding of molecular signalling and cellular interactions in the microenvironment of each organ and tissue is needed in order to define the best time to administer MSCs. Another challenge would be to mitigate the heterogeneity of the profile of cultured MSCs through preconditioning approaches. CONCLUSIONS: Cellular therapy with MSCs is very promising and should be part of the treatment of AKI patients in combination with other approaches already available, helping to accelerate recovery and/or slow the progression to chronic kidney disease. Randomized, multicentre controlled studies are needed to develop robust protocols that validate population-based cell therapy with MSCs.


Subject(s)
Humans , Animals , Mesenchymal Stem Cell Transplantation/trends , Acute Kidney Injury/therapy , Mesenchymal Stem Cells , Kidney/physiopathology , Tissue Distribution , Mesenchymal Stem Cell Transplantation/methods
5.
Article in Chinese | WPRIM | ID: wpr-878791

ABSTRACT

In this study, the chemical profiling of Jingyin Granules and the tissue distribution of nine major constituents in this Chinese medicine were performed after oral administration of Jingyin Granules to rats, by using UHPLC-Q-Exactive Orbitrap HR-MS. An Acquity UPLC BEH C_(18) chromatographic column(2.1 mm×100 mm, 1.7 μm) was used as solid phase, while the mobile phase was methanol and 0.1% formic acid water for gradient elution. The major constituents in this Chinese medicine were quickly and accurately identified, via comparison with the retention times and MS/MS spectra of the standards. A total of 106 chemicals were identified from Jingyin Granules, including 24 kinds of organic acids, 47 kinds of flavonoids, 10 kinds of iridoids, and 21 kinds of saponins and 4 kinds of other compounds. After oral administered Jingyin Granules to rats, 48, 30, 25, 23, 45, 34, 39, 26, 19 prototype compounds were identified in serum, heart, liver, spleen, lung, kidney, brain, fat, and testicles, respectively. Meanwhile, an LC-MS based analytical method was established for simultaneous determination of chlorogenic acid, swertiamarin, caffeic acid, sweroside, liquiritin, prim-O-glucosylcimifugin, arctiin, 5-O-methylvisammioside and arctigenin in biological samples. The tissue distribution(serum, liver and lung) of these nine aim constituents in rats after oral administration of Jingyin Granules were investigated. It was found that these nine constituents could be quickly absorbed into circulation system and then distributed to liver and lung tissues. Except arctigenin, the exposure of other eight aim constituents to serum and lung was peaked at 1 h. At 1 h, the exposure of these components to lung tissue were ranked as follows: swertiamarin [(75 191.0±3 483.21) ng·g~(-1)]>arctiin [(2 716.5±36.06) ng·g~(-1)]>5-O-methylvisammioside [(585.1±0.71) ng·g~(-1)]>arctigenin [(437.45±3.18) ng·g~(-1)]>chlorogenic acid [(308.1±5.66) ng·g~(-1)]>prim-O-glucosylcimifugin [(211.35±2.19) ng·g~(-1)]>sweroside [(184.3±9.05) ng·g~(-1)]>caffeic acid [(175.95±2.05) ng·g~(-1)]>liquiritin [(174.78±153.34) ng·g~(-1)]. In summary, an UHPLC-Q-Exactive Orbitrap HR-MS method has been established for rapid and accurate identification of the constituents in Jingyin Granules, while the tissue distribution of nine major absorpted constituents were investigated in rats following oral administration of Jingyin Granules. These findings provided key information and guidance for further studies on pharmacodynamic substances and clinical applications of Jingyin Granules.


Subject(s)
Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Rats , Tandem Mass Spectrometry , Tissue Distribution
6.
Article in Chinese | WPRIM | ID: wpr-773677

ABSTRACT

Cytochrome P450 family is a kind of biocatalyst widely existing in nature. It has many functions such as catalyzing the biosynthesis of plant secondary metabolites and regulating phytoremediation. Based on the analysis of proteome data of Tripterygium wilfordii,the CYP450 gene of T. wilfordii was preliminarily analyzed and predicted by various bioinformatics methods. The results showed that after the expression of T. wilfordii suspension cells was induced by methyl jasmonate,the proteomic data of T. wilfordii were obtained and analyzed,and 10 CYP450 proteins of T. wilfordii were finally screened out. By analyzing the phylogenetic tree constructed with CYP450 gene of Arabidopsis family,the 10 CYP450 proteins were clustered into 6 different CYP450 families. The physical and chemical properties of CYP450 proteins in different families were different. The secondary structure of CYP450 proteins was mainly composed of irregular curls. Eight subcellular localization results of CYP450 proteins were chloroplasts and the rest were plastids. Subsequently,the conserved domains( heme active sites) shared by CYP450 genes were found by analyzing the results of multiple sequence alignment. Finally,by analyzing the transcriptome data of T. wilfordii,the expression distribution of T. wilfordii in different tissues was preliminarily confirmed,which verified its correlation with the biosynthesis of active components of T. wilfordii,and provided important genetic resources for the analysis of biosynthesis pathway of active components of T. wilfordii.


Subject(s)
Computational Biology , Cytochrome P-450 Enzyme System , Chemistry , Phylogeny , Plant Proteins , Chemistry , Proteomics , Tissue Distribution , Tripterygium
7.
Article in Chinese | WPRIM | ID: wpr-773251

ABSTRACT

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.


Subject(s)
Acetylcysteine , Pharmacology , Administration, Intranasal , Animals , Biological Availability , Brain , Brain Chemistry , Chromatography, Liquid , Curcumin , Pharmacokinetics , Rats , Tandem Mass Spectrometry , Tissue Distribution
8.
Article in English | WPRIM | ID: wpr-773600

ABSTRACT

Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher C and AUC values (P < 0.05) in type 2 diabetic rats than that in normal rats and the tissue-distribution behaviors of the six flavonoid compounds in hearts, livers, spleens, lungs, kidneys, brains, pancreas, fat and muscle of the type 2 diabetic rats showed obviously differences from the normal rats (P < 0.05). In conclusion, the differences in the pharmacokinetics of oroxyloside and tissue distribution of the six flavanoids in Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.


Subject(s)
Administration, Oral , Animals , Chromatography, High Pressure Liquid , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Chemistry , Flavonoids , Chemistry , Pharmacokinetics , Male , Molecular Structure , Plant Roots , Chemistry , Rats , Rats, Wistar , Reproducibility of Results , Scutellaria baicalensis , Chemistry , Tandem Mass Spectrometry , Tissue Distribution , Physiology
9.
Article in Chinese | WPRIM | ID: wpr-771734

ABSTRACT

Artesunate, which is a widely used anti-malaria medicine, can be made into liposome to overcome its poor bioactivity. Its tissue distribution in rats may change with different dosage forms, which therefore shall be studied after ARS-TPGS-Lipo was injected. Based on this experiment, ARS-TPGS-Lipo and ARS-Lipo were prepared by thin-film hydration method. LC-MS/MS method was used to simultaneously determine ARS and DHA in rat tissues at different time points. The results showed that this method was suitable for the content analysis of ARS and DHA in biological samples. The distribution of ARS and DHA in ARS-TPGS-Lipo, ARS-Lipo and ARS groups were quite different. The content of ARS-TPGS-Lipo in liver was the highest, with significant differences.ARS and DHA contents in ARS group eliminated rapidly. ARS and DHA contents in ARS-Lipo group were higher in liver and spleen, while those in ARS-TPGS-Lipo group significantly increased only in liver (<0.05).


Subject(s)
Animals , Artesunate , Pharmacokinetics , Chromatography, Liquid , Liposomes , Rats , Tandem Mass Spectrometry , Tissue Distribution , Vitamin E
10.
Article in English | WPRIM | ID: wpr-812389

ABSTRACT

Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher C and AUC values (P < 0.05) in type 2 diabetic rats than that in normal rats and the tissue-distribution behaviors of the six flavonoid compounds in hearts, livers, spleens, lungs, kidneys, brains, pancreas, fat and muscle of the type 2 diabetic rats showed obviously differences from the normal rats (P < 0.05). In conclusion, the differences in the pharmacokinetics of oroxyloside and tissue distribution of the six flavanoids in Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.


Subject(s)
Administration, Oral , Animals , Chromatography, High Pressure Liquid , Diabetes Mellitus, Experimental , Drug Therapy , Metabolism , Drugs, Chinese Herbal , Chemistry , Flavonoids , Chemistry , Pharmacokinetics , Male , Molecular Structure , Plant Roots , Chemistry , Rats , Rats, Wistar , Reproducibility of Results , Scutellaria baicalensis , Chemistry , Tandem Mass Spectrometry , Tissue Distribution , Physiology
11.
Protein & Cell ; (12): 15-32, 2018.
Article in English | WPRIM | ID: wpr-756990

ABSTRACT

There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life. Most mAbs display target mediated drug disposition (TMDD), which can have significant consequences on the study designs of preclinical and clinical studies. The PK of mAb can also be influenced by anti-drug antibody (ADA) response and off-target binding, which require careful consideration during the discovery stage. mAbs are primarily absorbed through the lymphatics via convection and can be conveniently administered by the subcutaneous (sc) route in large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb can be reasonably estimated using cynomolgus monkey data and allometric scaling methods.


Subject(s)
Absorption, Physiological , Animals , Antibodies, Monoclonal , Pharmacokinetics , Dose-Response Relationship, Immunologic , Humans , Receptors, Fc , Metabolism , Recombinant Fusion Proteins , Pharmacokinetics , Tissue Distribution
12.
Article in English | WPRIM | ID: wpr-741521

ABSTRACT

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320–400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.


Subject(s)
Animals , Drug Delivery Systems , Fluorescence , Hyaluronic Acid , Kidney , Liver , Lung , Lymph Nodes , Mice , Nanoparticles , Pharmacokinetics , Spleen , Sublingual Gland , Testis , Tissue Distribution , Toxicokinetics
13.
Article in English | WPRIM | ID: wpr-311338

ABSTRACT

Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone, knee joints, and costal cartilage) were significantly higher than those in the heart, liver, and kidneys (P < 0.05). The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system (thighbone and costal cartilage) were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.


Subject(s)
Animals , Bone and Bones , Chemistry , Metabolism , Rats , Rats, Sprague-Dawley , T-2 Toxin , Pharmacokinetics , Toxicity , Tissue Distribution , Toxicity Tests, Acute
14.
Article in English | WPRIM | ID: wpr-728590

ABSTRACT

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the “fit for purpose” application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in C(max) of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.


Subject(s)
Area Under Curve , Caffeine , Ciprofloxacin , Computer Simulation , Drug Discovery , Humans , In Vitro Techniques , Permeability , Pharmacokinetics , Solubility , Tissue Distribution
15.
Article in English | WPRIM | ID: wpr-109782

ABSTRACT

Tissue distribution of marbofloxacin was studied in pigs after a single intramuscular injection at 2.5 mg/kg body weight. Samples of plasma, muscle, liver, kidney, heart, lung, and muscle at the injection site were randomly collected from five pigs at 2, 6, 10, 24, 48, 72, and 96 h after administration. Marbofloxacin concentrations were determined by using high-performance liquid chromatography with ultraviolet detection and were subjected to non-compartmental analysis to obtain kinetic parameters. The elimination half-life (t(1/2λz)) of marbofloxacin at the injection site was 22.12 h, while those in kidney, plasma, liver, lung, heart, and muscle were 16.75, 21.48, 21.84, 24.00, 24.45, and 28.91 h, respectively. Areas under the concentration-time curve from 0 h to (∞) (AUC(0–∞)s) were calculated to be 31.17 h·µg·mL⁻¹ for plasma and 32.97, 33.92, 34.78, 37.58, 42.02, and 98.80 h·µg·g⁻¹ for heart, muscle, lung, liver, kidney, and injection site, respectively. The peak concentration (C(max)) of marbofloxacin was 1.62 µg/mL in plasma and 1.71, 1.74, 1.86, 1.93, 2.45, and 7.64 µg/g in heart, lung, muscle, kidney, liver, and injection site, respectively. The results show that marbofloxacin was fast absorbed, extensively distributed, and slowly eliminated from pigs after a single intramuscular administration.


Subject(s)
Body Weight , Chromatography, Liquid , Half-Life , Heart , Injections, Intramuscular , Kidney , Liver , Lung , Plasma , Swine , Tissue Distribution
16.
Braz. j. biol ; 76(1): 194-204, Feb. 2016. tab, graf
Article in English | LILACS | ID: lil-774517

ABSTRACT

Abstract In this study, concentrations of trace elements in tissues of shrimp species (Litopenaeus vannamei) from farming and zone natural coastal located in the northeastern Brazil were investigated. The elements determination was performed by optical emission spectrometry with inductively coupled plasma (ICP OES). The following ranges of concentrations in the tissues were obtained in µg g–1 dry weight: Al: 13.4-886.5, Cd: 0.93-1.80; Cu: 24.8-152; Fe: 3.2-410.9; Mn: 0.36-24.4; Se: 0.094-9.81 and Zn: 20.3-109.4. The shrimp muscle can be a good iron source (about 88.9 mg–1g dry weight). The distribution of Se concentration in tissues showed much variation between locations, and the concentration levels found in shrimp muscles of wild samples were high, where its levels in 67% of muscle and 50% of others tissues samples exceeded the ANVISA limit, indicating evidence of selenium bioaccumulation. Significant correlation was observed between the following pairs of elements: Fe-Zn (r= –0.70), Mn-Cu (r= –0.74), Se-Cu (r= –0.68), Se-Mn (r= 0.82) in the muscles; Fe-Al (r= 0.99), Mn-Al (r= 0.62), Mn-Fe (r= 0.62), Se-Al (r = 0.88), Se-Fe (r= 0.87), Se-Mn (r= 0.58) in the exoskeleton and Cu-Zn (r = 0.68), Al-Cu (r= 0.88), Fe-Cu (r= 0.95) and Fe-Al (r= 0.97) in the viscera.


Resumo Esse estudo teve como objetivo avaliar as concentrações de elementos traço em tecidos da espécie de camarão Litopenaeus vannamei coletadas da zona costeira e de carciniculturas localizadas no nordeste do Brasil. Os elementos químicos foram determinados por espectrômetro de emissão óptica com plasma indutivamente acoplado (ICP OES). Foram encontradas as seguintes faixas de concentrações desses elementos nos tecidos (em mg g–1 peso seco): Al: 13,4-886,5; Cd: 0,93-1,80; Cu: 24,8-152; Fe: 3,2-4109; Mn: 0,36-24,4; Se: 0,094-9,81 and Zn: 20,3-109,4. O músculo do camarão investigado pode ser uma boa fonte de ferro (cerca de 88.9 mg-1g peso seco). A distribuição da concentração de Se nos tecidos apresentou muita variação entre as localidades, com níveis acima do estabelecido pela ANVISA para 67% dos musculos e 50% dos outros tecidos investigados, indicando evidências de bioacumulação do selênio. Houve correlações significativas entre os seguintes pares de elementos:: Fe-Zn (r= –0,70), Mn-Cu (r= –0,74), Se-Cu (r= –0,68), Se-Mn (r= 0,82) nos músculos, Fe-Al (r= 0,99), Mn-Al e Mn-Fe (r= 0,62), Se-Al (r = 0,88), Se-Fe (r= 0,87), Se-Mn (r= 0,58) no exoesqueleto e Cu-Zn (r = 068), Al-Cu (r= 0,88), Fe-Cu (r= 0,95) and Fe-Al (r= 0,97) nas vísceras.


Subject(s)
Animals , Penaeidae/physiology , Trace Elements/metabolism , Aquaculture , Brazil , Spectrophotometry, Atomic , Tissue Distribution
17.
Braz. j. pharm. sci ; 51(3): 643-651, July-Sept. 2015. tab, graf
Article in English | LILACS | ID: lil-766304

ABSTRACT

The aim of the present study was to investigate the tissue distribution and excretion of five components of Portulaca oleracea L. extract (POE) in rat following oral administration. A rapid, sensitive and specific ultra-high performance liquid chromatography (UHPLC) method with puerarin as the internal standard was used for the quantitative analysis of five components of POE, including caffeic acid (CA), p-coumaric acid (p-CA), ferulic acid (FA), quercitrin (QUER) and hesperidin (HP) in rat tissues including the liver, intestine, stomach, muscle, heart, lung, brain, kidney and spleen, urine and feces. The results show that onlyp-CA and FA were found in nearly all tissues with low cumulative ratios, and CA was higher in the intestine and stomach with a slightly higher cumulative ratio in the urine and feces after 24 h. HP and QUER were found at low levels in the tissues with low cumulative ratios.


O objetivo do presente estudo foi investigar a distribuição tecidual e excreção de cinco componentes de extrato Portulaca oleracea L. (POE) em ratos após administração oral. Um método analítico rápido, sensível e específico para quantificação de cinco componentes de POE (ácido cafeico (CA), ácidop-cumárico (p-CA), ácido ferúlico (FA), quercitrina (QUER) e hesperidina (HP)) por cromatografia líquida de ultra eficiência (UHPLC), empregando puerarina como padrão interno de referência. Os compostos foram quantificados em diferentes tecidos dos animais, sendo eles fígado, intestino, estômago, músculo, coração, pulmão, cérebro, rim e baço, urina e fezes. Os resultados mostraram que apenas p-CA e FA foram encontradas em todos os tecidos com baixas taxas cumulativas e CA apresentou níveis mais altos no intestino e estômago com a taxa cumulativa um pouco mais elevada na urina e nas fezes após 24 h. HP e QUER apresentaram baixas concentrações nos tecidos com baixas taxas cumulativas.


Subject(s)
Rats , Chromatography, Liquid/statistics & numerical data , Portulaca/classification , Rats , Phenolic Compounds , Tissue Distribution
18.
Rev. chil. pediatr ; 86(4): 244-250, ago. 2015. tab
Article in Spanish | LILACS | ID: lil-764080

ABSTRACT

Objetivo: Caracterizar la hospitalización por episodios de cianosis en recién nacidos (RN) > 34 semanas. Pacientes y método: Estudio retrospectivo que incluyó la totalidad de los RN hospitalizados por episodios de cianosis entre enero de 2007 y diciembre de 2012. En ellos se aplicaron 2 protocolos de estudio que consideraban exámenes de primera y segunda línea; estos últimos ante la recurrencia de eventos. El protocolo de primera línea consideró exámenes bioquímicos generales, radiografía de tórax y ecocardiografía en casos seleccionados, en tanto que el protocolo de segunda línea incluyó electroencefalograma, electrocardiograma, resonancia magnética nuclear encefálica, screening metabólico ampliado, ácido pirúvico, ácido láctico y en caso de convulsiones, citoquímico y cultivo de líquido cefalorraquídeo y reacción en cadena de la polimerasa para herpes. Resultados: Noventa y ocho de un total de 3.454 (2,8%) RN hospitalizados ingresaron por episodio de cianosis. La edad gestacional (EG) fue 37,8 + 1,36 semanas; peso al nacimiento: 3145 + 477 g. Edad materna: 32 + 4,8 años. El 19,4% de las madres tenía antecedentes mórbidos: diabetes gestacional (8,1%), síndrome hipertensivo del embarazo (5,1%), colestasia intrahepática (3,1%) y retardo del crecimiento (3,1%). Género: 48,8% masculino, parto por cesárea: 68,4%. Edad al ingreso: 1,9 + 1,4 días; duración de la hospitalización: 4,2 + 4,2 días. En todos los pacientes se practicaron exámenes de primera línea y en el 39,8% exámenes de segunda línea. En el 21,4% de los RN se identificó una causa, siendo el síndrome convulsivo el más frecuente (33%). Los RN con diagnóstico asociado presentaron 3,8 + 2,7 episodios de cianosis versus 1,5 + 2,4 en el grupo sin diagnóstico (NS). El 15,4% se fueron de alta con monitor; no hubo reingresos. Conclusión: La incidencia de hospitalización neonatal por episodios de cianosis fue de 6 por 1.000 RN vivos. Solo en cerca de un 20% de ellos es posible identificar una causa, siendo la más frecuente el síndrome convulsivo.


Objectives: A retrospective study was performed between January 2007 and December 2012 to assess the admission rates of newborns due to episodes of cyanosis Patients and method: Retrospective study that included all the newborns hospitalized with episodes of cyanosis between January 2007 and December 2012. In them were employed two study protocols that considered first and second line tests, the latter in view of recurrence of events. The first line protocol considered general biochemical tests, chest x-ray and echocardiography in selected cases, while the second line protocol included electroencephalogram, electrocardiogram, nuclear magnetic resonance of the brain, expanded metabolic screening, pyruvic acid, lactic acid, and in case of seizures, cytochemical, and culture of cerebrospinal fluid (CSF) and PCR (polymerase chain reaction) for herpes. Results: A total of 98 (2.8%) out of 3,454 newborns were admitted due to episodes of cyanosis. Gestational age: 37.8 + 1.4 weeks, birth weight: 3,145 + 477 g. Maternal age: 32 + 4.8 years. Disease was present in 19.4% of mothers; gestational diabetes (8.1%), pregnancy induced hypertension (5.1%), intrahepatic cholestasis (3.1%), and intrauterine growth retardation (3.1%). Gender: 48.8% male, 51.2% female (NS). Birth: caesarean section, 68.4%, and vaginal delivery, 31.6%. Age on admission 1.9 + 1.4 days. Hospital stay: 4.2 + 4.2 days. First line tests were performed in 100% of patients with 39.8% fulfilling the criteria for second line study. A condition was detected in 21.4%, with convulsive syndrome was the most frequent (33%). Newborns with an identified condition had 3.8 + 2.7episodes versus 1.5 + 2,4 in those without diagnosis (NS). A home oxygen monitor was given to 15.4%. There were no re-admissions. Conclusions: Most newborns admitted due to cyanosis are discharged with a condition of unknown origin. In this study, convulsive syndrome was the most frequent cause.


Subject(s)
Animals , Female , Mice , Drug Carriers/chemistry , Epirubicin/chemistry , Epirubicin/pharmacology , Nanoparticles/chemistry , Neoplasms/drug therapy , Silicon Dioxide/chemistry , Cell Line, Tumor , Drug Delivery Systems/methods , Mice, Inbred BALB C , Particle Size , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Porosity , Tissue Distribution
19.
Braz. j. biol ; 75(3s1): 106-111, Aug. 2015. tab, graf
Article in English | LILACS | ID: lil-769577

ABSTRACT

Abstract Studies using chelonians as biosentinels of environment quality or health risks associated with turtle consumption are very rare, especially in the Amazon basin. This study aims to measure Mercury levels (Hg) in muscle, liver, fat and blood of Podocnemis unifilis from the lower Xingu River, assessing the possible difference in concentration between sexes and also evaluating the potential bioaccumulation along different body sizes. Samples were collected during the dry season (October 2012) and Mercury (Hg) concentrations were analysed by Cold Vapor Atomic Absorption Spectrometry (CVAAS). A total of 29 specimens of P. unifilis of different sizes showed low levels lower than 0.2 mg/Kg). Higher Hg concentrations were found in the liver, and significant correlations between Hg concentrations in the different tissues were also detected. There was no difference between males and females and a negative correlation was found between Hg concentration and body size.


Resumo Estudos utilizando quelônios como biosentinelas de qualidade ambiental ou de riscos à saúde associados ao consumo de tartarugas são raros, especialmente na bacia amazônica. Neste estudo foram medidos os níveis de mercúrio no músculo, fígado, gordura e sangue de Podocnemis unifilis do baixo Rio Xingu. Foram avaliadas as possíveis diferenças de concentração entre os sexos e também o potencial de bioacumulação ao longo de diferentes tamanhos corporais. A etapa de amostragem ocorreu durante o período seco (Outubro de 2012) e a quantificação de Mercúrio (Hg) foi realizada através de digestão ácida e análises por Espectrometria de Absorção Atômica com Vapor Frio (CVAAS). Um total de 29 amostras de Podocnemis unifilis, mesmo em diferentes tamanhos, mostraram concentrações de Hg menores que 0,2 mg/kg. As concentrações mais elevadas de Hg foram encontradas no fígado, e também foram detectadas correlações significativas entre as concentrações de Hg nos tecidos. Não foram observadas diferenças significativas entre machos e fêmeas, sendo registrada correlação negativa entre a concentração de Hg e o tamanho do corpo.


Subject(s)
Animals , Female , Male , Mercury/metabolism , Turtles/metabolism , Water Pollutants, Chemical/metabolism , Body Size , Brazil , Rivers , Seasons , Tissue Distribution
20.
Clinics ; 70(3): 162-168, 03/2015. tab, graf
Article in English | LILACS | ID: lil-747103

ABSTRACT

PURPOSE: To compare the characteristics of tubercular vs. leukemic involvement of abdominopelvic lymph nodes using multidetector computed tomography (CT). MATERIALS AND METHODS: We retrospectively reviewed multidetector computed tomography features including lymph node size, shape, enhancement patterns, and anatomical distribution, in 106 consecutive patients with newly diagnosed, untreated tuberculosis (55 patients; 52%) or leukemia (51 patients; 48%). In patients with leukemia, 32 (62.7%) had chronic lymphocytic leukemia, and 19 (37.3%) had acute leukemias; of these, 10 (19.6%) had acute myeloid leukemia, and 9 (17.6%) had acute lymphocytic leukemia. RESULTS: The lower para-aortic (30.9% for tuberculosis, 63.2% for acute leukemias and 87.5% for chronic lymphocytic leukemia) and inguinal (9.1% for tuberculosis, 57.9% for acute leukemias and 53.1% for chronic lymphocytic leukemia) lymph nodes were involved more frequently in the three types of leukemia than in tuberculosis (both with p <0.017). Tuberculosis showed peripheral enhancement, frequently with a multilocular appearance, in 43 (78.2%) patients, whereas patients with leukemia (78.9% for acute myeloid leukemia and acute lymphocytic leukemia, 87.5% for chronic lymphocytic leukemia) demonstrated predominantly homogeneous enhancement (both with p <0.017). For the diagnosis of tuberculosis, the analysis showed that a peripheral enhancement pattern had a sensitivity of 78.2%, a specificity of 100%, and an accuracy of 88.7%. For the diagnosis of leukemia, the analysis showed that a homogeneous enhancement pattern was associated with a sensitivity of 84.3%, a specificity of 94.5%, and an accuracy of 89.6%. CONCLUSION: Our findings indicate that the anatomical distribution and enhancement patterns of lymphadenopathy seen on multidetector computed tomography are useful for differentiating between untreated tuberculosis and leukemia of the abdominopelvic lymph nodes. .


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/therapy , Cone-Beam Computed Tomography/methods , Ethiodized Oil/pharmacokinetics , Liver Neoplasms/metabolism , Liver Neoplasms/therapy , Multidetector Computed Tomography/methods , Antineoplastic Agents/therapeutic use , Chemoembolization, Therapeutic , Carcinoma, Hepatocellular , Ethiodized Oil/therapeutic use , Hemostatics/therapeutic use , Imaging, Three-Dimensional/methods , Liver Neoplasms , Metabolic Clearance Rate , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution , Treatment Outcome
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