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 ® (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 ® . Following a 21 h permeation study, the highest total amount of MTZ permeated through the rat healthy and disturbed skin was seen with Rozex ® , 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 ® , when the stratum corneum was present as a barrier. In conclusion, thermogel formulations can be favorable alternatives to Rozex ® for the topical application of MTZ with improved efficacy and reduced side effects.Uniterms: Metronidazole/evaluation. Metronidazole/drug retention. Poloxamer 407. Rosacea/treatment. Dermatopharmacokinetic.

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 desta 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 mostram 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.

Conventional pharmacokinetic profiles of drugs are described mainly by plotting drug plasma concentration versus time. However, topical drugs are designed to target local tissue and, as such, have limited systemic absorption. For these drugs, the pharmacokinetic measurements in the local tissue (skin) are of more importance than systemic measurements. In this context, this study aims to develop and discuss the appropriate bioanalytical methodology by high performance liquid chromatography (HPLC) and application to ex vivo DPK metronidazole (MTZ) study based on the resolution-RE no. 899/2003 and Collegiate Board Resolution-RDC no. 27/2012 guidelines from the National Health Surveillance Agency of Brazil (ANVISA) and the FDA Guidance for Industry Bioanalytical Method Validation (2013). The average of recovery was 98.71% in a linear range from 0.1 to 20 μg/mL. The intraday and interday precision and accuracy were within specified limits to bioanalytical methods. MTZ was not detected in the receptor solution after 6 h, demonstrating that during this time, the drug is not able to cross the skin at a flow, resulting in a concentration higher than 0.1 μg/mL, which is the lower limit of quantification of this method. The amount of MTZ found in the pig SC was 20.91±7.02 µg/cm 2 (n=14). Based on these results, it can be concluded that the validation of the drug dosage methodology described here was sensitive, precise and accurate and was successfully applied to analyze ex vivo DPK samples and is an important step for ensuring the reliability of these analyses.