scholarly journals Pharmacokinetics of Benznidazole in Experimental Chronic Chagas Disease Using the Swiss mouse-Berenice-78 Trypanosoma cruzi Strain Model

2020 ◽  
Author(s):  
Suzana Marques de Jesus ◽  
Leonardo Pinto ◽  
Fernanda de Lima Moreira ◽  
Glauco Henrique Balthazar Nardotto ◽  
Rodrigo Cristofoletti ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Chronic Infection ◽  
High Performance ◽  
Array Detector ◽  
Dosing Regimen ◽  
Penetration Ratio ◽  
Parameter Values ◽  
Strain Model ◽  
Old Mice ◽  
Chronic Chagas Disease

Chronic Chagas disease might have an impact on benznidazole pharmacokinetics with potential alterations in the therapeutic dosing regimen. The study aims to investigate the influence of chronic T. cruzi infection on the pharmacokinetics and biodistribution of benznidazole in mice. Healthy (n = 40) and chronically T. cruzi (Berenice-78 strain) infected (n = 40) Swiss female 10-month old mice received a single oral dose of 100 mg/kg benznidazole. Serial blood, heart, colon and brain samples were collected up to 12 h after benznidazole administration. The serum and tissues samples were analyzed using a High Performance Liquid Chromatography instrument coupled to a diode array detector. The chronic infection by T. cruzi increased the following pharmacokinetic parameter values Ka (3.92 vs 1.82 h−1), Vd/F (0.089 vs 0.036 L) and CL/F (0.030 vs 0.011 liters/h), and reduced the values of Tmax (0.67 vs 1.17 h) and t 1/2a (0.18 vs 0.38 h). The tissue exposure (AUC0-t,tissue) was longer and higher in the chronic infected mice in colon (8.15 vs 21.21 μg h/g) and heart (5.72 vs 13.58 μg h/g). The chronic infection also increased 1.6; 3.25 and 3 times of the benznidazole tissue penetration ratio (AUC0-t, tissue/AUC0-t, serum) of brain, colon and heart, respectively. The experimental chronic Chagas disease inflammation-mediated changes in the regulation of membrane transporters, probably influence the benznidazole pharmacokinetics and extent benznidazole exposure in the tissues. These results advise for potential alterations in benznidazole pharmacokinetics in chronic Chagas disease patients with possibilities of changes in the standard dosing regimen.

scholarly journals Population Pharmacokinetics of Benznidazole in Adult Patients with Chagas Disease

2015 ◽  
Vol 59 (6) ◽  
pp. 3342-3349 ◽  
Author(s):  
D. Soy ◽  
E. Aldasoro ◽  
L. Guerrero ◽  
E. Posada ◽  
N. Serret ◽  
...  
Keyword(s):  
Chagas Disease ◽  
High Performance ◽  
Time Course ◽  
Plasma Concentrations ◽  
Apparent Volume ◽  
Biological Data ◽  
Target Range ◽  
Population Pharmacokinetic ◽  
Open Label ◽  
Chronic Chagas Disease

ABSTRACTThe aim of the present study was to build a population pharmacokinetic (popPK) model to characterize benznidazole (BNZ) pharmacokinetics in adults with chronic Chagas disease. This study was a prospective, open-label, single-center clinical trial approved by the local ethics committee. Patients received BNZ at 2.5 mg/kg of body weight/12 h (Abarax, Elea Laboratory, Argentina) for 60 days. Plasma BNZ samples were taken several times during the study and analyzed by high-performance liquid chromatography with UV-visible detection (HPLC-UV). The popPK analysis was done with NONMEMv.7.3. Demographic and biological data were tested as covariates. Intraindividual, interoccasion, and residual variabilities were modeled. Internal and external validations were completed to assess the robustness of the model. Later on, simulations were performed to generate BNZ concentration-time course profiles for different dosage regimens. A total of 358 plasma BNZ concentrations from 39 patients were included in the analysis. A one-compartment PK model characterized by clearance (CL/F) and the apparent volume of distribution (V/F), with first-order absorption (Ka) and elimination, adequately described the data (CL/F, 1.73 liters/h;V/F, 89.6 liters; andKa, 1.15 h−1). No covariates were found to be significant for CL/FandV/F. Internal and external validations of the final model showed adequate results. Data from simulations revealed that a dose of 2.5 mg/kg/12 h might lead to overexposure in most patients. A lower dose (2.5 mg/kg/24 h) was able to achieve trough BNZ plasma concentrations within the accepted therapeutic range of 3 to 6 mg/liter. In summary, we developed a population PK model for BNZ in adults with chronic Chagas disease. Dosing simulations showed that a BNZ dose of 2.5 mg/kg/24 h will adequately keep BNZ trough plasma concentrations within the recommended target range for the majority of patients. (This study has been registered at EudraCT under number 2011-002900-34 and at ClinicalTrials.gov under number NCT01755403.)

Simultaneous Determination of Six Components in Jingzhiguanxin Tablet by High-Performance Liquid Chromatography

2019 ◽  
Vol 15 (2) ◽  
pp. 130-137
Author(s):  
Hui Jiang ◽  
Lianhao Fu ◽  
Yu Wang ◽  
Shaozhi Wang ◽  
Xiaoxu Zhang ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Gradient Elution ◽  
Tanshinone Iia ◽  
Array Detector ◽  
Control Analysis ◽  
Active Components ◽  
Quality Control Analysis

Background: Jingzhiguanxin (JZGX) tablet, a traditional Chinese prescription, is commonly used for treating coronary heart disease and angina pectoris in the clinic. There are six active components (Danshensu (DSS), Protocatechuic aldehyde (PD), Paeoniflorin (PF), Ferulic acid (FA), Salvianolic acid B (Sal B) and Tanshinone IIA (TA)) in JZGX tablet. </P><P> Objective: In this paper, a simple and reliable method was used for simultaneous determining the six active components by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Methods: These six active components were separated on an Agilent Zorbax Eclipse XDB-C18 column (150 mmx4.6 mm, 5 µm) at 30 °C. Acetonitrile (A), methanol (B) and 0.5% H3PO4 aqueous solution (C) were used as mobile phase for gradient elution. The flow rate was 1 mL/min and the detection wavelengths were set at 280 nm for DSS, PD and Sal B, 230 nm for PF, 320 nm for FA and 270 nm for TA, respectively. Results: All of the six components showed good linearity regressions (r2≥0.9997) in the detected concentration range. The recovery rates and coefficient of variation (CV) for all analytes were 98.66%- 100.18% and 0.75%-1.89%, respectively. This method was successfully applied to simultaneously determine the six components in JZGX tablet from different batches and manufacturers. Conclusion: The validated method can be used in routine quality control analysis of JZGX tablet without any interference.

Supramolecular Solvent Based Liquid-Liquid Microextraction for Preconcentration of Selected Fluoroquinolone Antibiotics in Environmental Water Sample Prior to High Performance Liquid Chromatographic Determination

2019 ◽  
Vol 15 (6) ◽  
pp. 607-615 ◽  
Author(s):  
Shirley K. Selahle ◽  
Philiswa N. Nomngongo
Keyword(s):  
High Performance ◽  
Chromatographic Determination ◽  
Decanoic Acid ◽  
Environmental Water ◽  
High Performance Liquid Chromatographic ◽  
Array Detector ◽  
Optimum Conditions ◽  
Limit Of Quantification ◽  
Supramolecular Solvent ◽  
Liquid Microextraction

Background and Objective: A rapid, simple and environmental friendly supramolecular solvent (SUPRAS) based liquid-liquid microextraction method for preconcentration of ciprofloxacin (CIPRO), danofloxacin (DANO) and enrofloxacin (ENRO) from wastewater was developed. Methods: This microextraction technique was coupled with high-performance liquid chromatography equipped with a diode array detector (HPLC-PDA) for detection and separation of the antibiotics. The SUPRAS composed of decanoic acid and tricaprylymethylammonium chloride. Optimum conditions for the extraction and preconcentration of all the antibiotics were obtained using surface response methodology (RSM) based on Box-Behnken design. Results: Under optimum conditions, the limits of detection (LOD) and limit of quantification (LOQ) ranged from 0.06-0.14 µg L−1 and 0.22-0.47 μg L−1, respectively with the preconcentration factors ranging from 153-241. The linear dynamic ranges were between LOQ and 850 µg L−1 with correlation coefficients ranging from 0.9928 to 0.9999. The intra-day (n = 15) and inter-day (n = 5) precisions (expressed in terms of %RSD) for 50 µg L−1 of CIPRO, DANO and ENRO were in the range of 3.3–4% and 4.1–5.8%, respectively. Conclusion: Lastly, the developed method was used for the extraction, preconcentration and quantification of selected CIPRO, DANO and ENRO in influent and effluent wastewater samples.

scholarly journals Simple HPLC-PDA Analysis to Determine Illegal Synthetic Dyes in Herbal Medicines

2021 ◽  
Vol 11 (14) ◽  
pp. 6641
Author(s):  
Kyung-Yuk Ko ◽  
Eun-Young Choi ◽  
Se-Hee Jeong ◽  
Sohwa Kim ◽  
Choon-Kil Lee ◽  
...  
Keyword(s):  
High Performance ◽  
Hplc Analysis ◽  
Ammonium Acetate ◽  
Herbal Medicines ◽  
Positive Sample ◽  
Array Detector ◽  
Synthetic Dyes ◽  
Sunset Yellow ◽  
Herbal Medication ◽  
Relative Standard

Various synthetic dyes are artificially added to herbal medicines for the purpose of visual attraction. In order to monitor the illegal usage of synthetic dyes in herbal medication, a rapid and straightforward analysis method to determine synthetic dyes is required. The study aimed to develop and validate a high-performance liquid chromatography (HPLC) analysis to determine ten synthetic dyes in Hawthorn fruit, Cornus fruit, and Schisandra fruit. Ten synthetic dyes such as Tartrazine, Sunset yellow, Metanil yellow, Auramine O, Amaranth, Orange II, Acid red 73, Amaranth, New Coccine, Azorubine, and Erythrosine B, were extracted using 50 mM ammonium acetate in 70% MeOH; then separated by gradient elution with a mobile phase consisting of acetonitrile and 50 mM ammonium acetate in distilled water using a photodiode array detector (PDA) at 428 nm or 500 nm. In addition, this study established the LC-MS/MS method to confirm the existence of synthetic dyes in the positive sample solution. The HPLC analysis had good linearity (r2 > 0.999). The recoveries of this method ranged from 74.6~132.1%, and the relative standard deviation (RSD) values were less than 6.9%. Most of the samples fulfilled the acceptance criteria of the AOAC guideline. This study demonstrates that the HPLC analysis can be applied to determine ten synthetic dyes in herbal medication.

scholarly journals Phytochemical variability during vegetation of Chamerion angustifolium (L.) Holub genotypes derived from in vitro cultures

2021 ◽  
Author(s):  
Mariola Dreger ◽  
Katarzyna Seidler-Łożykowska ◽  
Milena Szalata ◽  
Artur Adamczak ◽  
Karolina Wielgus
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Array Detector ◽  
Reproduction Rate ◽  
Full Spectrum ◽  
Breeding Programs ◽  
Chamerion Angustifolium ◽  
Oenothein B

AbstractThe purpose of the study was to evaluate Chamerion angustifolium (L.) Holub genotypes for preliminary selection and further breeding programs aimed at obtaining a suitable industrial form for the pharmaceutical applications. Clonally propagated plants representing 10 genotypes of Ch. angustifolium were regenerated under in vitro conditions, hardened and planted in the field. Studies included an evaluation of shoot proliferation, phytochemical assessment of in vitro and ex vitro plants as well as investigations of intraspecies variability regarding four phenological stages: vegetative, beginning of blooming, full blooming, and green fruit phases. Quantitative and qualitative analyses of bioactive compounds were performed using high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometer (HPLC–DAD–MS/MS) and high-performance liquid chromatography (HPLC) methods. The efficiency of shoot multiplication varied between genotypes from 8.12 to 21.48 shoots per explant. A high reproduction rate (> 20 shoots per explant) was recorded for four lines (PL_45, PL_44, PL_58, DE_2). Plants grown in vitro synthesized oenothein B (11.2–22.3 mg g−1 DW) and caffeic acid derivatives. Plants harvested from field contained the full spectrum of polyphenols characteristic for this species, and oenothein B and quercetin 3-O-glucuronide were the most abundant. The maximal content of oenothein B was determined in the vegetative phase of fireweed, while some flavonoids were found in the highest amount in full blooming phase. The results of analysis of variance indicated significant differences among genotypes in oenothein B, 3-O-caffeoylquinic acid and flavonoids accumulation in four phenological phases. PL_44 plants were characterized by high content of oenothein B and quercetin 3-O-glucuronide as well as a relatively high level of other flavonoids. Based on our phytochemical and micropropagation studies, PL_44 genotype was the best candidate for early selection and further breeding programs.

Effects of repetitive stress during the acute phase ofTrypanosoma cruziinfection on chronic Chagas' disease in rats

Stress ◽  
2009 ◽  
Vol 12 (2) ◽  
pp. 144-151 ◽  
Author(s):  
Leony Cristina Caetano ◽  
Vânia Brazão ◽  
Marina Del Vecchio Filipin ◽  
Fabricia Helena Santello ◽  
Luana Naiara Caetano ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Acute Phase ◽  
Repetitive Stress ◽  
Chronic Chagas Disease
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