RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jabora... more RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jabora... more RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
Analytical and Bioanalytical Chemistry, Apr 18, 2008
Instability in film coating formulations can arise from interactions between aluminum lake pigmen... more Instability in film coating formulations can arise from interactions between aluminum lake pigments and aqueous polymeric dispersions. The purpose of this study was to characterize the interactions between three polymethacrylate-based aqueous polymeric dispersions (Eudragit 1 RS 30 D, Eudragit 1 L 30 D-55, and Eudragit 1 NE 30 D) and aluminum lakes. Particle size measurements, pH stability profiles, zeta potential measurements, and microscopy were used to study mixed dispersions of the polymeric latices and the lakes. Interactions leading to dispersion instability were related to the surface charge of the components in the formulation. Interactions between the ionic polymers and the lakes arose from instability of the lakes outside a certain pH range resulting in the release of electrolytes, which led to aggregation of the polymeric particles. Interactions between the nonionic polymer and the lakes were related to the polymer modifying the surface charge of the lakes, resulting in aggregation of the pigment particles.
Trichilia catigua A. Juss., Meliaceae, known as catuaba in Brazil, is traditionally used for the ... more Trichilia catigua A. Juss., Meliaceae, known as catuaba in Brazil, is traditionally used for the treatment of stress, sexual impotence and memory deficits. To our knowledge, there is no analytical method described in literature for simultaneous quantification of catuaba extract marker substances in biological matrices. The aim of this study was to develop and validate a bioanalytical method by LC-MS/MS to quantify epicatechin and procyanidin B2 in rat plasma after administration of standardized extract of T. catigua. Chromatographic separation was achieved with a C18 column, methanol and 0.1% aqueous formic acid at a flow rate of 0.25 ml/min. Detection was performed using electrospray ionization in negative mode. The lower limits of quantification were 5 ng/ml and 12.5 ng/ml for procyanidin B2 and epicatechin, respectively. Intra-and inter-day assays variability were less than 15%. The extraction recovery was 104% for epicatechin and 74% for procyanidin B2 using one-step liquid-liquid extraction with ethyl acetate. Epicatechin and PB2 were detected in plasma up to 300 min after oral administration of 400 mg/kg of standardized extract of T. catigua in rats. This rapid and sensitive method for the analysis of the epicatechin and procyanidin B2 in rat plasma can be applied to pharmacokinetic studies.
Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown ... more Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.
Pediatric drugs knowledge still leaves several gaps to be filled, all the while many biopharmaceu... more Pediatric drugs knowledge still leaves several gaps to be filled, all the while many biopharmaceutic properties applied to adults do not work in pediatrics. The solubility in many cases is extrapolated to pediatrics; however, sometimes it may not represent the real scenario. In this context, the aim of this study was to assess the possibility of the extrapolation of the solubility data assumed for adults to children aged 2–12 years using lamotrigine (LTG) as a model. LTG showed that its solubility is dependent on the pH of the medium, no precipitate formation was seen, and biomimetic media showed a greater capacity to solubilize it. Based on the dose number (D0) in adults, the LTG was soluble in acidic pH media and poorly soluble in neutral to basic. Similar behavior was found in conditions which mimic children aged 10–12 years at a dose of 5 and 15 mg/kg. The D0 for 5‐year‐old children at a dose of 15 mg/kg showed different behaviors between biorelevant and pharmacopeial buffers media. For children aged 2–3 years, LTG appeared to be poorly soluble under both gastric and intestinal conditions. Solubility was dependent on the volume of fluid calculated for each age group, and this may impact the development of better pharmaceutical formulations for this population, better pharmacokinetic predictions in tools as PBPK, and physiologically‐based biopharmaceutics modeling, greater accuracy in the justifications for biowaiver, and many other possibilities.
The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the phy... more The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the physiological changes after "Roux-en-Y gastric bypass" (RYGB) surgery in bariatric patients, was evaluated. A middle-out approach for parameter estimations was undertaken using in vitro, in situ, and in vivo data. The observed versus predicted plasma concentrations and the model sensitivity of the simulated parameters of AUC0-inf and Cmax of amoxicillin (AMX) were used to confirm the reliability of the estimation. The model considers that a drug-transporter (Transp) in the initial segments of the normal intestine plays a significant role in the AMX absorption. A lower fraction absorbed (Fabs) was observed in RYGB patients (54.43 % for suspension and 45.21 % for tablets) compared to healthy subjects (77.48 % capsule). Furthermore, the tablet formulation presented a lower dissolved fraction (Fd) and Fabs compared to the suspension formulation of AMX in RYGB patients (91.70 % and 45.21 % versus 99.92 % and 54.43 %, respectively). The AUC0-inf and Cmax were sensitive to changes in Rtintestine, PeffAMX, and Transp for both healthy and RYGB models. Additionally, AUC0-inf and Cmax were also sensitive to changes in the tlag parameter for tablet formulation in RYGB patients. The PBPK Model showed a reduction in AMX bioavailability as a consequence of reduced intestinal length after RYGB surgery. Additionally, the difference in the predicted Fd and Fabs between suspension and tablet suggests that liquid formulations are preferable in post-bariatric patients.
Uma das principais funcoes do farmaceutico, ao exercer um programa de atencao farmaceutica, e dia... more Uma das principais funcoes do farmaceutico, ao exercer um programa de atencao farmaceutica, e diagnosticar problemas relacionados a medicamentos (PRMs), resolve-los e preveni-los. PRM e definido com sendo um evento ou circunstância indesejavel que envolve a farmacoterapia do paciente e que potencialmente interfere com a habilidade deste paciente alcancar os resultados medicamentosos previstos ou separados, podendo ter consequencias patologicas, psicologicas, sociais e economicas (Strand, Morley, Cipolle et al., 1990).
RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jabora... more RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known ... more Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known as Revatio® and approved for the treatment of pulmonary arterial hypertension. Maternal administration of sildenafil during pregnancy is being evaluated for antenatal treatment of several conditions, including the prevention of pulmonary hypertension in fetuses with congenital diaphragmatic hernia. However, determination of a safe and effective maternal dose to achieve adequate fetal exposure to sildenafil remains challenging, as pregnancy almost always is an exclusion criterion in clinical studies. Physiologically-based pharmacokinetic (PBPK) modelling offers an attractive approach for dose finding in this specific population. The aim of this study is to exploit physiologically-based pharmacokinetic modelling to predict the required maternal dose to achieve therapeutic fetal exposure for the treatment congenital diaphragmatic hernia. A full-PBPK model was developed for sildenafil and N-...
As informações sobre a absorção de flavonóides ainda são muito controversas e na sua grande maior... more As informações sobre a absorção de flavonóides ainda são muito controversas e na sua grande maioria os estudos foram realizados com O-heterosídeos, flavonóides bastante instáveis. Para o estudo de previsão de absorção de flavonóide foi utilizado a vicenina-2, que é um flavonóide C-heterosídeo, com atividade antinflamatório. A relação entre retenção-atividade (QRAR) usando a cromatografia micelar de biopartição (BMC) foi a técnica empregada para atingir tal objetivo. Os resultados deste método in vitro foram comparados com resultados obtidos em ensaios in vivo de permeação intestinal em ratos obtendo-se as mesmas taxas de absorção de 60%. A taxa de união a proteínas plasmáticas foi avaliada por eletroforese capilar (EC) e indicou uma relação entre estrutura-taxa de união a albumina (HSA). A presença ou a disponibilidade da hidroxila em C3 do anel C do flavonóide parece ser determinante para altas taxas de união a HSA, e as substituições no anel B não demonstraram importantes relações...
The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the phy... more The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the physiological changes after "Roux-en-Y gastric bypass" (RYGB) surgery in bariatric patients, was evaluated. A middle-out approach for parameter estimations was undertaken using in vitro, in situ, and in vivo data. The observed versus predicted plasma concentrations and the model sensitivity of the simulated parameters of AUC 0-inf and C max of amoxicillin (AMX) were used to confirm the reliability of the estimation. The model considers that a drug-transporter (Transp) in the initial segments of the normal intestine plays a significant role in the AMX absorption. A lower fraction absorbed (F abs) was observed in RYGB patients (54.43 % for suspension and 45.21 % for tablets) compared to healthy subjects (77.48 % capsule). Furthermore, the tablet formulation presented a lower dissolved fraction (F d) and F abs compared to the suspension formulation of AMX in RYGB patients (91.70 % and 45.21 % versus 99.92 % and 54.43 %, respectively). The AUC 0-inf and C max were sensitive to changes in R tintestine , Peff AMX , and Transp for both healthy and RYGB models. Additionally, AUC 0inf and C max were also sensitive to changes in the t lag parameter for tablet formulation in RYGB patients. The PBPK Model showed a reduction in AMX bioavailability as a consequence of reduced intestinal length after RYGB surgery. Additionally, the difference in the predicted F d and F abs between suspension and tablet suggests that liquid formulations are preferable in post-bariatric patients.
Através do estabelecimento da correlação entre as concentrações livres do antibiótico no tecido i... more Através do estabelecimento da correlação entre as concentrações livres do antibiótico no tecido infectado (responsáveis pela morte bacteriana), obtidas por microdiálise, e as concentrações plasmáticas totais, pode-se utilizar a amostragem sanguínea para inferir as variações teciduais do fármaco obtidas com diferentes posologias. O objetivo deste trabalho foi adaptar e validar metodologia de Cromatografia Líquida de Alta Eficiência (CLAE) para o doseamento de piperacilina, antibiótico b-lactâmico, em plasma e dialisado de tecido muscular infectado de ratos. O método foi desenvolvido utilizando-se coluna de fase reversa RP 18 e mistura de tampão fosfato 0,05 M:acetonitrila (80:20, v/v) como fase móvel, com fluxo de 1mL/min e detecção a 220 nm. Para análise do dialisado, adicionou-se quantidades conhecidas de piperacilina à solução de Ringer e injetou-se diretamente 20 µL no cromatógrafo. Para análise do plasma, adicionou-se quantidades conhecidas de piperacilina a 100 µL de plasma de rato, precipitou-se as proteínas com 200 µL de acetonitrila contendo ácido p-aminobenzóico (padrão interno). Injetou-se alíquotas de 100 µL do sobrenadante no aparelho. Os dois métodos serão validados através da determinação da variabilidade inter e intradiária, utilizando-se amostras de controle de qualidade. Resultados preliminares mostram tempo de retenção da piperacilina de 7 min e padrão interno, 13 min. As curvas de calibração são lineares na faixa de 1 a 20 µg/mL (dialisado) e 2 a 500 µg/mL (plasma), com limite de quantificação de 0.7 µg/mL e 1 µg/mL, respectivamente. A metodologia obtida parece adequada para utilização na quantificação de piperacilina em amostras de dialisado de tecido e plasma de ratos, que constitue a próxima etapa do projeto.
As concentrações sangüíneas totais de antimicrobianos estão apenas indiretamente relacionadas com... more As concentrações sangüíneas totais de antimicrobianos estão apenas indiretamente relacionadas com a cura das infecções. O efeito antimicrobiano no local da infecção é obtido pelas concentrações livres. A determinação das concentrações livres do
Resumo O trabalho em desenvolvimento busca orientar tecnicamente agricultoras familiares do assen... more Resumo O trabalho em desenvolvimento busca orientar tecnicamente agricultoras familiares do assentamento de Reforma Agrária Iraci Salete de Alvorada do Sul - PR, no cultivo de plantas medicinas, voltadas à produção de chás e fitoterápicos, com o objetivo de geração de ...
RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jabora... more RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jabora... more RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
Analytical and Bioanalytical Chemistry, Apr 18, 2008
Instability in film coating formulations can arise from interactions between aluminum lake pigmen... more Instability in film coating formulations can arise from interactions between aluminum lake pigments and aqueous polymeric dispersions. The purpose of this study was to characterize the interactions between three polymethacrylate-based aqueous polymeric dispersions (Eudragit 1 RS 30 D, Eudragit 1 L 30 D-55, and Eudragit 1 NE 30 D) and aluminum lakes. Particle size measurements, pH stability profiles, zeta potential measurements, and microscopy were used to study mixed dispersions of the polymeric latices and the lakes. Interactions leading to dispersion instability were related to the surface charge of the components in the formulation. Interactions between the ionic polymers and the lakes arose from instability of the lakes outside a certain pH range resulting in the release of electrolytes, which led to aggregation of the polymeric particles. Interactions between the nonionic polymer and the lakes were related to the polymer modifying the surface charge of the lakes, resulting in aggregation of the pigment particles.
Trichilia catigua A. Juss., Meliaceae, known as catuaba in Brazil, is traditionally used for the ... more Trichilia catigua A. Juss., Meliaceae, known as catuaba in Brazil, is traditionally used for the treatment of stress, sexual impotence and memory deficits. To our knowledge, there is no analytical method described in literature for simultaneous quantification of catuaba extract marker substances in biological matrices. The aim of this study was to develop and validate a bioanalytical method by LC-MS/MS to quantify epicatechin and procyanidin B2 in rat plasma after administration of standardized extract of T. catigua. Chromatographic separation was achieved with a C18 column, methanol and 0.1% aqueous formic acid at a flow rate of 0.25 ml/min. Detection was performed using electrospray ionization in negative mode. The lower limits of quantification were 5 ng/ml and 12.5 ng/ml for procyanidin B2 and epicatechin, respectively. Intra-and inter-day assays variability were less than 15%. The extraction recovery was 104% for epicatechin and 74% for procyanidin B2 using one-step liquid-liquid extraction with ethyl acetate. Epicatechin and PB2 were detected in plasma up to 300 min after oral administration of 400 mg/kg of standardized extract of T. catigua in rats. This rapid and sensitive method for the analysis of the epicatechin and procyanidin B2 in rat plasma can be applied to pharmacokinetic studies.
Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown ... more Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.
Pediatric drugs knowledge still leaves several gaps to be filled, all the while many biopharmaceu... more Pediatric drugs knowledge still leaves several gaps to be filled, all the while many biopharmaceutic properties applied to adults do not work in pediatrics. The solubility in many cases is extrapolated to pediatrics; however, sometimes it may not represent the real scenario. In this context, the aim of this study was to assess the possibility of the extrapolation of the solubility data assumed for adults to children aged 2–12 years using lamotrigine (LTG) as a model. LTG showed that its solubility is dependent on the pH of the medium, no precipitate formation was seen, and biomimetic media showed a greater capacity to solubilize it. Based on the dose number (D0) in adults, the LTG was soluble in acidic pH media and poorly soluble in neutral to basic. Similar behavior was found in conditions which mimic children aged 10–12 years at a dose of 5 and 15 mg/kg. The D0 for 5‐year‐old children at a dose of 15 mg/kg showed different behaviors between biorelevant and pharmacopeial buffers media. For children aged 2–3 years, LTG appeared to be poorly soluble under both gastric and intestinal conditions. Solubility was dependent on the volume of fluid calculated for each age group, and this may impact the development of better pharmaceutical formulations for this population, better pharmacokinetic predictions in tools as PBPK, and physiologically‐based biopharmaceutics modeling, greater accuracy in the justifications for biowaiver, and many other possibilities.
The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the phy... more The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the physiological changes after "Roux-en-Y gastric bypass" (RYGB) surgery in bariatric patients, was evaluated. A middle-out approach for parameter estimations was undertaken using in vitro, in situ, and in vivo data. The observed versus predicted plasma concentrations and the model sensitivity of the simulated parameters of AUC0-inf and Cmax of amoxicillin (AMX) were used to confirm the reliability of the estimation. The model considers that a drug-transporter (Transp) in the initial segments of the normal intestine plays a significant role in the AMX absorption. A lower fraction absorbed (Fabs) was observed in RYGB patients (54.43 % for suspension and 45.21 % for tablets) compared to healthy subjects (77.48 % capsule). Furthermore, the tablet formulation presented a lower dissolved fraction (Fd) and Fabs compared to the suspension formulation of AMX in RYGB patients (91.70 % and 45.21 % versus 99.92 % and 54.43 %, respectively). The AUC0-inf and Cmax were sensitive to changes in Rtintestine, PeffAMX, and Transp for both healthy and RYGB models. Additionally, AUC0-inf and Cmax were also sensitive to changes in the tlag parameter for tablet formulation in RYGB patients. The PBPK Model showed a reduction in AMX bioavailability as a consequence of reduced intestinal length after RYGB surgery. Additionally, the difference in the predicted Fd and Fabs between suspension and tablet suggests that liquid formulations are preferable in post-bariatric patients.
Uma das principais funcoes do farmaceutico, ao exercer um programa de atencao farmaceutica, e dia... more Uma das principais funcoes do farmaceutico, ao exercer um programa de atencao farmaceutica, e diagnosticar problemas relacionados a medicamentos (PRMs), resolve-los e preveni-los. PRM e definido com sendo um evento ou circunstância indesejavel que envolve a farmacoterapia do paciente e que potencialmente interfere com a habilidade deste paciente alcancar os resultados medicamentosos previstos ou separados, podendo ter consequencias patologicas, psicologicas, sociais e economicas (Strand, Morley, Cipolle et al., 1990).
RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jabora... more RESUMO: A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.
Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known ... more Sildenafil is a potent vasodilator and phosphodiesterase type five inhibitor, commercially known as Revatio® and approved for the treatment of pulmonary arterial hypertension. Maternal administration of sildenafil during pregnancy is being evaluated for antenatal treatment of several conditions, including the prevention of pulmonary hypertension in fetuses with congenital diaphragmatic hernia. However, determination of a safe and effective maternal dose to achieve adequate fetal exposure to sildenafil remains challenging, as pregnancy almost always is an exclusion criterion in clinical studies. Physiologically-based pharmacokinetic (PBPK) modelling offers an attractive approach for dose finding in this specific population. The aim of this study is to exploit physiologically-based pharmacokinetic modelling to predict the required maternal dose to achieve therapeutic fetal exposure for the treatment congenital diaphragmatic hernia. A full-PBPK model was developed for sildenafil and N-...
As informações sobre a absorção de flavonóides ainda são muito controversas e na sua grande maior... more As informações sobre a absorção de flavonóides ainda são muito controversas e na sua grande maioria os estudos foram realizados com O-heterosídeos, flavonóides bastante instáveis. Para o estudo de previsão de absorção de flavonóide foi utilizado a vicenina-2, que é um flavonóide C-heterosídeo, com atividade antinflamatório. A relação entre retenção-atividade (QRAR) usando a cromatografia micelar de biopartição (BMC) foi a técnica empregada para atingir tal objetivo. Os resultados deste método in vitro foram comparados com resultados obtidos em ensaios in vivo de permeação intestinal em ratos obtendo-se as mesmas taxas de absorção de 60%. A taxa de união a proteínas plasmáticas foi avaliada por eletroforese capilar (EC) e indicou uma relação entre estrutura-taxa de união a albumina (HSA). A presença ou a disponibilidade da hidroxila em C3 do anel C do flavonóide parece ser determinante para altas taxas de união a HSA, e as substituições no anel B não demonstraram importantes relações...
The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the phy... more The potential of a PBPK model to predict oral Amoxicillin bioavailability, by considering the physiological changes after "Roux-en-Y gastric bypass" (RYGB) surgery in bariatric patients, was evaluated. A middle-out approach for parameter estimations was undertaken using in vitro, in situ, and in vivo data. The observed versus predicted plasma concentrations and the model sensitivity of the simulated parameters of AUC 0-inf and C max of amoxicillin (AMX) were used to confirm the reliability of the estimation. The model considers that a drug-transporter (Transp) in the initial segments of the normal intestine plays a significant role in the AMX absorption. A lower fraction absorbed (F abs) was observed in RYGB patients (54.43 % for suspension and 45.21 % for tablets) compared to healthy subjects (77.48 % capsule). Furthermore, the tablet formulation presented a lower dissolved fraction (F d) and F abs compared to the suspension formulation of AMX in RYGB patients (91.70 % and 45.21 % versus 99.92 % and 54.43 %, respectively). The AUC 0-inf and C max were sensitive to changes in R tintestine , Peff AMX , and Transp for both healthy and RYGB models. Additionally, AUC 0inf and C max were also sensitive to changes in the t lag parameter for tablet formulation in RYGB patients. The PBPK Model showed a reduction in AMX bioavailability as a consequence of reduced intestinal length after RYGB surgery. Additionally, the difference in the predicted F d and F abs between suspension and tablet suggests that liquid formulations are preferable in post-bariatric patients.
Através do estabelecimento da correlação entre as concentrações livres do antibiótico no tecido i... more Através do estabelecimento da correlação entre as concentrações livres do antibiótico no tecido infectado (responsáveis pela morte bacteriana), obtidas por microdiálise, e as concentrações plasmáticas totais, pode-se utilizar a amostragem sanguínea para inferir as variações teciduais do fármaco obtidas com diferentes posologias. O objetivo deste trabalho foi adaptar e validar metodologia de Cromatografia Líquida de Alta Eficiência (CLAE) para o doseamento de piperacilina, antibiótico b-lactâmico, em plasma e dialisado de tecido muscular infectado de ratos. O método foi desenvolvido utilizando-se coluna de fase reversa RP 18 e mistura de tampão fosfato 0,05 M:acetonitrila (80:20, v/v) como fase móvel, com fluxo de 1mL/min e detecção a 220 nm. Para análise do dialisado, adicionou-se quantidades conhecidas de piperacilina à solução de Ringer e injetou-se diretamente 20 µL no cromatógrafo. Para análise do plasma, adicionou-se quantidades conhecidas de piperacilina a 100 µL de plasma de rato, precipitou-se as proteínas com 200 µL de acetonitrila contendo ácido p-aminobenzóico (padrão interno). Injetou-se alíquotas de 100 µL do sobrenadante no aparelho. Os dois métodos serão validados através da determinação da variabilidade inter e intradiária, utilizando-se amostras de controle de qualidade. Resultados preliminares mostram tempo de retenção da piperacilina de 7 min e padrão interno, 13 min. As curvas de calibração são lineares na faixa de 1 a 20 µg/mL (dialisado) e 2 a 500 µg/mL (plasma), com limite de quantificação de 0.7 µg/mL e 1 µg/mL, respectivamente. A metodologia obtida parece adequada para utilização na quantificação de piperacilina em amostras de dialisado de tecido e plasma de ratos, que constitue a próxima etapa do projeto.
As concentrações sangüíneas totais de antimicrobianos estão apenas indiretamente relacionadas com... more As concentrações sangüíneas totais de antimicrobianos estão apenas indiretamente relacionadas com a cura das infecções. O efeito antimicrobiano no local da infecção é obtido pelas concentrações livres. A determinação das concentrações livres do
Resumo O trabalho em desenvolvimento busca orientar tecnicamente agricultoras familiares do assen... more Resumo O trabalho em desenvolvimento busca orientar tecnicamente agricultoras familiares do assentamento de Reforma Agrária Iraci Salete de Alvorada do Sul - PR, no cultivo de plantas medicinas, voltadas à produção de chás e fitoterápicos, com o objetivo de geração de ...
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