Metronidazole thermogel improves retention and decreases permeation through the skin

Metronidazole (MTZ) is widely used as the standard antibiotic for the treatment of rosacea and, more recently, is being used off label in Brazilian hospitals for the treatment of wounds. Following oral administration, minimal amounts of active agent reaches the skin and side effects are strongly induced. Consequently, MTZ is currently being applied topically in order to improve the therapeutic efficacy with reduced side effects, with Rozex(r) (RZ) (an MTZ gelled formulation) being the only marketed product. This study examined whether the use of MTZ 0.75% from thermogel formulations could improve drug retention and reduce dermal exposure compared to that by Rozex(r). Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex(r), but similar to all formulations regardless of the skin condition. On the other hand, the amount retained in the epidermis/dermis was larger for thermogel formulations; at least 4 fold that of Rozex(r), when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex(r) for the topical application of MTZ with improved efficacy and reduced side effects

Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment

Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml1. Intra- and interday precision and bias values were less than 14.87% (n 9) and 9.81% (n 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.Fil: Galindo Bedor, Danilo César. Universidade Federal de Pernambuco; BrasilFil: Tavares Cavalcanti Bedor, Noely Camila. No especifíca;Fil: Wellithom Viturino da Silva, José. Universidade Federal de Pernambuco; BrasilFil: Damasceno Sousa, Giovana. Universidade Federal de Pernambuco; BrasilFil: Pereira de Santana, Davi. Universidade Federal de Pernambuco; BrasilFil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blum, Bethania. No especifíca;Fil: Alves, Fabiana. No especifíca;Fil: Ribeiro, Isabela. No especifíca

Quality evaluation of a Brazilian marketed herbal medicine made from Schinus terebinthifolius Raddi: changes in the legislation for registration throughout 20 years / Avaliação da qualidade de um medicamento à base Schinus terebinthifolius Raddi (aroeira) comercializado no Brasil: adequação à legislação ao longo de 20 ano

Considering the importance of the evaluation of quality and performance attributes of herbal medicines, this work evaluated a gynecological gel containing aroeira (Schinus terebinthifolius Raddi), which was previously registered in 2001, and is still marketed in Brazil. Using the updated guides and legislation as a basis, the product was evaluated by checking the pH, spreadability, rheological behavior, in vitro release test, ex vivo permeation and retention study using porcine vaginal mucosa in Franz diffusion cells, and histological evaluation of the porcine vaginal mucosa before and after application of the product. After the permeation study, it was verified that gallic acid (chemical marker quantified) does not cross the mucosa, therefore, it is safe for local use. In addition, the pH of the formulation is within the range considered normal for use in healthy women. Finally, the histological evaluation of the mucosa showed changes compatible with the application of tannins (major compounds of the plant), and without changes indicative of loss of tissue integrity.

Influência do gênero em estudos de bioequivalência de medicamentos

As diferenças anatômicas e fisiológicas entre os gêneros masculino e feminino podem modificar o processo farmacocinético de um fármaco e assim, interferir em sua biodisponibilidade, tornando um determinado medicamento não bioequivalente quando comparado em apenas um gênero. Dito isto, o objetivo deste trabalho foi avaliar a influência do gênero na bioequivalência de três medicamentos testes na forma de comprimido revestido: Metildopa 500 mg, Diazepam 10 mg e Butilbrometo de Escopolamina 10mg. Para tanto, os parâmetros farmacocinéticos que determinam a bioequivalência, ASC0-t, ASC0-∞ e Cmáx, foram recalculados considerando os gêneros em separado. Os estudos do Diazepam e Escopolamina foram bioequivalentes para ambos os sexos, mas bioinequivalentes quando considerado apenas o sexo feminino. O estudo de bioequivalência da Metildopa não foi bioequivalente para ambos os sexos e nem para os sexos em separado. Assim, faz se necessário ampliar as discussões sobre a forma de analisar e definir a bioequivalência de medicamentos a fim de garantir a eficiência e segurança dos tratamentos para ambos os sexos

Uso tópico do cidofovir para tratamento das lesões associadas ao Papillomavírus humano: revisão da literatura

As verrugas genitais são lesões epiteliais induzidas pelo Papillomavirus Humano (HPV). Atualmente, as técnicas utilizadas para tratamento dessas lesões são dolorosas e as recidivas costumam acontecer em um curto espaço de tempo. Diversos estudos têm demonstrado a eficácia do cidofovir no tratamento de HPV entre outras infecções virais. O objetivo dessa revisão de literatura é fazer uma abordagem sobre o fármaco e a sua utilização clínica no tratamento de HPV, apresentando a forma farmacêutica, posologia, reações adversas e dados sobre sua eficácia. Os resultados da pesquisa bibliográfica mostraram que o uso intralesional e epidérmico do cidofovir em formulações extemporâneas tem se mostrado eficaz no manejo dos condilomas. A utilização tópica do cidofovir se apresenta, portanto, como uma alternativa clínica aos tratamentos convencionais, minimizando os efeitos colaterais locais e evitando a ocorrência de efeitos adversos sistêmicos. Diante disso, faz-se necessária a padronização de uma formulação tópica através de estudos de pré-formulação e demais ensaios clínicos visando a obtenção de uma preparação estável, segura e eficaz para tratamento das lesões associadas ao HPV