Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e22452
Horieh Hajhashemi, Somayeh Taymouri, F. Shafiee
Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.
{"title":"Development and evaluation of wafer loaded with sertaconazole solid dispersion for the treatment of oral candidiasis","authors":"Horieh Hajhashemi, Somayeh Taymouri, F. Shafiee","doi":"10.1590/s2175-97902023e22452","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22452","url":null,"abstract":"Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e22381
Gabriel Nóbrega da Costa, L. Y. Queiroz, Isaque Nilton dos Santos, H. I. Cimarosti
According to the World Health Organization (WHO), the elderly population (> 60 years old) will increase from 12% in 2015 to 22% in 2050 and projections indicate that in 2030 there will be 1.4 billion people aged 60 years and over. This increment in the populational age represents not only a social demographic problem but also a medical one (Rudnicka et al., 2020). Aging is one of the main risk factors for several neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases (AD, PD, and HD, respectively) (Kritsilis et al., 2018). AD affects approximately 55 million people worldwide and is more frequent between 75 and 84 years old (Alzheimer’s Association, 2021; WHO, 2022), whereas PD is the second most prevalent neurodegenerative disease affecting 2-3% of the population over 65 years old (Poewe et al., 2017). Moreover, HD, which affects 5 to 7 individuals per 100,000 inhabitants aged between 30 and 50 years (Bruzelius et al., 2019), is also an important neuropathology (Shawki et al., 2021). In a simplified way, AD, PD, and HD mainly impair neuronal structures and functions in part due to the aberrant accumulation of certain aggregated proteins: amyloid-beta (Aβ) in AD, α-synuclein in PD (Kulenkampff et al., 2021;Shawki et al., 2021), and huntingtin (HTT) in Neuroprotective potential of the Amazonian fruits Euterpe oleracea Mart. and Paullinia cupana Kunth
根据世界卫生组织(世卫组织)的数据，老年人口(60岁以上)将从2015年的12%增加到2050年的22%，预测表明，到2030年，60岁及以上的人口将达到14亿。人口年龄的增长不仅是一个社会人口问题，也是一个医学问题(Rudnicka et al.， 2020)。衰老是几种神经退行性疾病的主要危险因素之一，包括阿尔茨海默病、帕金森病和亨廷顿病(分别为AD、PD和HD) (Kritsilis et al.， 2018)。阿尔茨海默病影响全球约5500万人，在75至84岁之间更为常见(阿尔茨海默病协会，2021年;世卫组织，2022)，而帕金森病是第二大最常见的神经退行性疾病，影响65岁以上人口的2-3% (Poewe等人，2017)。此外，每10万名30至50岁的居民中有5至7人患有HD (Bruzelius等人，2019)，这也是一种重要的神经病理学(Shawki等人，2021)。简而言之，AD、PD和HD主要损害神经元结构和功能，部分原因是某些聚集蛋白的异常积累:AD中的淀粉样蛋白- β (a β)， PD中的α-突触核蛋白(Kulenkampff et al.， 2021;Shawki et al.， 2021)和亚马逊水果Euterpe oleracea Mart的神经保护潜能中的亨廷顿蛋白(HTT)。和Paullinia cupana Kunth
{"title":"Neuroprotective potential of the Amazonian fruits Euterpe oleracea Mart. and Paullinia cupana Kunth","authors":"Gabriel Nóbrega da Costa, L. Y. Queiroz, Isaque Nilton dos Santos, H. I. Cimarosti","doi":"10.1590/s2175-97902023e22381","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22381","url":null,"abstract":"According to the World Health Organization (WHO), the elderly population (> 60 years old) will increase from 12% in 2015 to 22% in 2050 and projections indicate that in 2030 there will be 1.4 billion people aged 60 years and over. This increment in the populational age represents not only a social demographic problem but also a medical one (Rudnicka et al., 2020). Aging is one of the main risk factors for several neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases (AD, PD, and HD, respectively) (Kritsilis et al., 2018). AD affects approximately 55 million people worldwide and is more frequent between 75 and 84 years old (Alzheimer’s Association, 2021; WHO, 2022), whereas PD is the second most prevalent neurodegenerative disease affecting 2-3% of the population over 65 years old (Poewe et al., 2017). Moreover, HD, which affects 5 to 7 individuals per 100,000 inhabitants aged between 30 and 50 years (Bruzelius et al., 2019), is also an important neuropathology (Shawki et al., 2021). In a simplified way, AD, PD, and HD mainly impair neuronal structures and functions in part due to the aberrant accumulation of certain aggregated proteins: amyloid-beta (Aβ) in AD, α-synuclein in PD (Kulenkampff et al., 2021;Shawki et al., 2021), and huntingtin (HTT) in Neuroprotective potential of the Amazonian fruits Euterpe oleracea Mart. and Paullinia cupana Kunth","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e22453
K. Chomaničová, Élida Alechaga Silva, R. Alemany
In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known—as well as hitherto unknown— trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0–4 h, 4–8 h, 8–12 h, and 12–24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites.
{"title":"Metabolic study of trimetazidine using ultra-high performance liquid chromatography-tandem mass spectrometry","authors":"K. Chomaničová, Élida Alechaga Silva, R. Alemany","doi":"10.1590/s2175-97902023e22453","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22453","url":null,"abstract":"In the present study, the application of ultra-high performance liquid chromatography-tandem mass spectrometry allowed us to study of known—as well as hitherto unknown— trimetazidine (TMZ) metabolites in human urine and to propose their renal excretion profiles. Urine samples from a healthy volunteer were analyzed at baseline and at 0–4 h, 4–8 h, 8–12 h, and 12–24 h after a single dose of TMZ. A dilute-and-shoot procedure was used as sample treatment before separation. Full-scan spectra of possible metabolites were acquired. Additionally, product ion scan spectra of precursor ions of interest were also acquired at two collision energies. Intact TMZ was a major excretion product, with a maximum concentration at 4-8 h after administration. Moreover, five minor metabolites were observed, namely trimetazidine-N-oxide (M1), N-formyl trimetazidine (M2), desmethyl-trimetazidine O-sulfate (M3), desmethyl-trimetazidine O-glucuronide (M4), and desmethyl-trimetazidine-N-oxide-O-glucuronide (M5). Metabolite M5 has not previously been reported. Excretion curves were constructed based on the chromatographic peak areas of specific mass transitions (precursor ion > product ion) related to each of the detected metabolites.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e22430
Elton Max Nascimento do Egito, Isaac Aaron Morales Frias, Maria D. L. Oliveira, César Augusto Souza de Andrade
Lipoprotein monitoring is desirable in the management of medical conditions such as atherosclerotic cardiovascular disease and coronary artery disease, in which controlling the concentration of these chylomicrons is crucial. Current clinical methods are complex and present poor reproducibility between laboratories. For these reasons, recent guidelines discard the assessment of low-density lipoprotein cholesterol (LDL-C) as a routine analysis during lipid-lowering therapies. Concerning the importance of monitoring this parameter, the authors present an electrochemical immunosensor constructed from a simple and easy-to-reproduce platform that allows detecting and quantifying LDL nanoparticles directly from human serum samples. The performance of the biosensor was studied by scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The biosensing platform displays good stability and linearity between 30 mg dL -1 and 135 mg dL -1 with a detection limit of 20 mg dL -1 . The proposed biosensor can be easily employed for monitoring LDL concentration in clinical treatments.
{"title":"Electrochemical immunosensing of low-density lipoprotein based on sol-gel encapsulation","authors":"Elton Max Nascimento do Egito, Isaac Aaron Morales Frias, Maria D. L. Oliveira, César Augusto Souza de Andrade","doi":"10.1590/s2175-97902023e22430","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22430","url":null,"abstract":"Lipoprotein monitoring is desirable in the management of medical conditions such as atherosclerotic cardiovascular disease and coronary artery disease, in which controlling the concentration of these chylomicrons is crucial. Current clinical methods are complex and present poor reproducibility between laboratories. For these reasons, recent guidelines discard the assessment of low-density lipoprotein cholesterol (LDL-C) as a routine analysis during lipid-lowering therapies. Concerning the importance of monitoring this parameter, the authors present an electrochemical immunosensor constructed from a simple and easy-to-reproduce platform that allows detecting and quantifying LDL nanoparticles directly from human serum samples. The performance of the biosensor was studied by scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The biosensing platform displays good stability and linearity between 30 mg dL -1 and 135 mg dL -1 with a detection limit of 20 mg dL -1 . The proposed biosensor can be easily employed for monitoring LDL concentration in clinical treatments.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e22106
Anna Kelly Moura-Silva, B. Mano-Sousa, Lays Pedrosa Santos, R. R. D. Costa, F. P. D. Andrade, J. M. Duarte-Almeida, D. Gonçalves
Guarana
{"title":"Development and validation of an analytical method by HPLC-DAD for determination of caffeine in products based on guarana extracts (Paullinia cupana)","authors":"Anna Kelly Moura-Silva, B. Mano-Sousa, Lays Pedrosa Santos, R. R. D. Costa, F. P. D. Andrade, J. M. Duarte-Almeida, D. Gonçalves","doi":"10.1590/s2175-97902023e22106","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22106","url":null,"abstract":"Guarana","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67741858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e211019
Fabio Tamanini, Beatriz Sakakibara Moraes, C. Amaral, A. Carvalho, E. Trovatti
The form of drug administration affects the success of treatment, since it can influence adherence of the patient to the therapy. The use of orodispersible films has emerged as a way to overcome some drawbacks of conventional methods of drug delivery, especially for patients experiencing difficulty in swallowing. These films are prepared using a matrix that incorporates the drug and contains other substances that confer the properties of the system. The present work describes the use of thermoplastic starch as a carrier for the model drug diclofenac, including film preparation and testing of its orodispersible potential. Preparation of the film employed a microwave oven to gelatinize and plasticize corn starch, with incorporation of the model drug, followed by solvent-casting. The samples were characterized using mechanical tests, analyses of water uptake and water content, and Fourier transform infrared spectroscopy. The results indicated that the film presented promising properties as an alternative system for oral drug administration, with good incorporation and distribution of the drug in the matrix. The material displayed satisfactory mechanical properties, which are crucial for this type of material, due to the need for oral administration and handling before use.
{"title":"Starch-based orodispersible film for diclofenac release","authors":"Fabio Tamanini, Beatriz Sakakibara Moraes, C. Amaral, A. Carvalho, E. Trovatti","doi":"10.1590/s2175-97902023e211019","DOIUrl":"https://doi.org/10.1590/s2175-97902023e211019","url":null,"abstract":"The form of drug administration affects the success of treatment, since it can influence adherence of the patient to the therapy. The use of orodispersible films has emerged as a way to overcome some drawbacks of conventional methods of drug delivery, especially for patients experiencing difficulty in swallowing. These films are prepared using a matrix that incorporates the drug and contains other substances that confer the properties of the system. The present work describes the use of thermoplastic starch as a carrier for the model drug diclofenac, including film preparation and testing of its orodispersible potential. Preparation of the film employed a microwave oven to gelatinize and plasticize corn starch, with incorporation of the model drug, followed by solvent-casting. The samples were characterized using mechanical tests, analyses of water uptake and water content, and Fourier transform infrared spectroscopy. The results indicated that the film presented promising properties as an alternative system for oral drug administration, with good incorporation and distribution of the drug in the matrix. The material displayed satisfactory mechanical properties, which are crucial for this type of material, due to the need for oral administration and handling before use.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"23 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67738600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.1590/s2175-97902023e22643
Chetna Modi, P. Bharadia
Transfersomes
{"title":"In-Vitro and Ex-Vivo Evaluation of Transfersomal Gel of Methotrexate","authors":"Chetna Modi, P. Bharadia","doi":"10.1590/s2175-97902023e22643","DOIUrl":"https://doi.org/10.1590/s2175-97902023e22643","url":null,"abstract":"Transfersomes","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67742673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.
{"title":"Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling","authors":"Zhi-Ping Jin, M. Yan, Si-Ze Li, Bao-Qing Wang, Qing-fang Xu, Wei Wu, Xiaoyang Li, Qian-zhou Lv, Xiao-Qiang Xiang","doi":"10.1590/s2175-97902023e21343","DOIUrl":"https://doi.org/10.1590/s2175-97902023e21343","url":null,"abstract":"Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"43 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67739723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-08DOI: 10.1590/s2175-97902023e21415
E. Costa, T. Castro, C. Gonçalves-de-Albuquerque, H. C. F. Faria Neto, J. Gonçalves, R. Estrela
Dasatinib, a potent oral multi-targeted kinase inhibitor against Src and Bcr-Abl, can decrease inflammatory response in sepsis. A simple and cost-effective method for determination of an effective dose dasatinib was established. This method was validated in human plasma, with the aim of reducing the number of animals used, thus, avoiding ethical problems. Dasatinib and internal standard lopinavir were extracted from 180 uL of plasma using liquid-liquid extraction with methyl tert-butil ether, followed by liquid chromatography coupled to triple quadrupole mass spectrometry in multiple reaction monitoring mode. For the pharmacokinetic study, 1 mg/kg of dasatinib was administered to mice with and without sepsis. The method was linear over the concentration range of 1-98 ng/mL for DAS in mice and human plasma, with r 2 >0.99 and presented intra-and interday precision within the range of 2.3 – 6.2 and 4.3 – 7.0%, respectively. Further intra-and interday accuracy was within the range of 88.2 – 105.8 and 90.6 – 101.7%, respectively. The mice with sepsis showed AUC0-t = 2076.06 h*ng/mL and Cmax = 102.73 ng/mL and mice without sepsis presented AUC0-t = 2128.46 h*ng/mL. Cmax = 164.5 ng/mL. The described analytical method was successfully employed in pharmacokinetic study of DAS in mice.
{"title":"Development and validation of liquid chromatography-tandem mass spectrometry method to quantify dasatinib in plasma and its application to a pharmacokinetic study","authors":"E. Costa, T. Castro, C. Gonçalves-de-Albuquerque, H. C. F. Faria Neto, J. Gonçalves, R. Estrela","doi":"10.1590/s2175-97902023e21415","DOIUrl":"https://doi.org/10.1590/s2175-97902023e21415","url":null,"abstract":"Dasatinib, a potent oral multi-targeted kinase inhibitor against Src and Bcr-Abl, can decrease inflammatory response in sepsis. A simple and cost-effective method for determination of an effective dose dasatinib was established. This method was validated in human plasma, with the aim of reducing the number of animals used, thus, avoiding ethical problems. Dasatinib and internal standard lopinavir were extracted from 180 uL of plasma using liquid-liquid extraction with methyl tert-butil ether, followed by liquid chromatography coupled to triple quadrupole mass spectrometry in multiple reaction monitoring mode. For the pharmacokinetic study, 1 mg/kg of dasatinib was administered to mice with and without sepsis. The method was linear over the concentration range of 1-98 ng/mL for DAS in mice and human plasma, with r 2 >0.99 and presented intra-and interday precision within the range of 2.3 – 6.2 and 4.3 – 7.0%, respectively. Further intra-and interday accuracy was within the range of 88.2 – 105.8 and 90.6 – 101.7%, respectively. The mice with sepsis showed AUC0-t = 2076.06 h*ng/mL and Cmax = 102.73 ng/mL and mice without sepsis presented AUC0-t = 2128.46 h*ng/mL. Cmax = 164.5 ng/mL. The described analytical method was successfully employed in pharmacokinetic study of DAS in mice.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67739746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-08DOI: 10.1590/s2175-97902023e201178
Mohd Basheeruddin, V. Lavanya, Neesar Ahmed, Shazia Jamal
Abstract Diclofenac sodium (DF) is a non-steroidal anti-inflammatory drug (NSAID) that possesses antipyretic, analgesic, antinociceptive and anti-inflammatory activities. Like other NSAIDs, DF is known to be associated with renal, cardiovascular, and gastrointestinal complications. The present study was carried out to evaluate the adverse effects of DF in vivo in wistar albino rats and to assess if oral administration of the organic osmolyte betaine mitigates the adverse effect of DF. Eighteen male Wistar rats were divided into three groups, one group of animals was fed orally with 20 mg/kg of DF once/day, and the other group received a combination of 20 mg/kg of DF and 30 mg/kg of betaine, once/day. Apart from the hematological and biochemical parameters, histopathological changes in the liver, lungs, brain, heart and kidney were also investigated. Histopathological alterations that were found in the liver, kidney, and lungs of DF-treated animals were found to be minimal or absent in DF + betaine-treated animals, as compared to untreated control. The results showed that betaine mitigates the adverse effects associated with DF treatment.
{"title":"Organic osmolyte betaine mitigates the deleterious effects of Diclofenac in vivo in wistar albino rats","authors":"Mohd Basheeruddin, V. Lavanya, Neesar Ahmed, Shazia Jamal","doi":"10.1590/s2175-97902023e201178","DOIUrl":"https://doi.org/10.1590/s2175-97902023e201178","url":null,"abstract":"Abstract Diclofenac sodium (DF) is a non-steroidal anti-inflammatory drug (NSAID) that possesses antipyretic, analgesic, antinociceptive and anti-inflammatory activities. Like other NSAIDs, DF is known to be associated with renal, cardiovascular, and gastrointestinal complications. The present study was carried out to evaluate the adverse effects of DF in vivo in wistar albino rats and to assess if oral administration of the organic osmolyte betaine mitigates the adverse effect of DF. Eighteen male Wistar rats were divided into three groups, one group of animals was fed orally with 20 mg/kg of DF once/day, and the other group received a combination of 20 mg/kg of DF and 30 mg/kg of betaine, once/day. Apart from the hematological and biochemical parameters, histopathological changes in the liver, lungs, brain, heart and kidney were also investigated. Histopathological alterations that were found in the liver, kidney, and lungs of DF-treated animals were found to be minimal or absent in DF + betaine-treated animals, as compared to untreated control. The results showed that betaine mitigates the adverse effects associated with DF treatment.","PeriodicalId":9218,"journal":{"name":"Brazilian Journal of Pharmaceutical Sciences","volume":"27 3 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67737044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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