RESUMO
Atropine is an antimuscarinic alkaloid identified in Atropa belladonna. In pharmacopeias, percolation is standardized as an extraction method for A. belladonna leaves, along with liquid-liquid extraction as a cleanup procedure and titration as an analytical method for assaying the atropine in the leaves. In this study, a faster, solvent-saving, and more reliable method for quality control of A. belladonna samples was developed. Ultrasound-assisted extraction was proposed and optimized by fractional factorial design followed by Box-Behnken design. For modeling atropine content, the following optimal conditions were established: particle size, 180 µm; percentage methanol in water, 50%; volume of solvent, 15 ml; time of extraction, 60 min; and number of extractions, two. This led to a significant improvement in atropine extraction (P < 0.001). For cleanup, solid-phase extraction was used as an alternative to liquid-liquid extraction, giving similar results, with higher reproducibility. Finally, for the atropine assay, a UPLC method was validated as a substitute for the classic titration method. Taken together, the development of an ultrasound-assisted extraction-solid-phase extraction-UPLC approach allowed the determination of atropine content in A. belladonna leaves in a time- and solvent-saving manner, with high reliability.
Assuntos
Atropa belladonna/química , Atropina/análise , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Folhas de Planta/química , Extração em Fase Sólida/métodos , Antagonistas Muscarínicos/análise , Solventes/químicaRESUMO
Antimuscarinic agents are the first-line choice for the treatment of neurogenic detrusor overactivity (NDO). The currently available antimuscarinic drugs have been widely studied in patients presenting idiopathic detrusor overactivity; however, investigations evaluating the effects of these drugs on NDO are scant, particularly with regard to cost-effectiveness analyses. A pharmacoeconomic evaluation was performed to compare the costs and effectiveness of oxybutynin and tolterodine in two different formulations, extended (ER) and immediate-release (IR), for the treatment of NDO (based on Brazilian maximal consumer price index). A systematic review of literature was conducted in order to obtain significant clinical and urodynamic data (based on expert opinion), concerning the effects of these drugs in the neurogenic population. Furthermore, a pharmacoeconomic evaluation was performed and costs involved were calculated based on percentage effectiveness obtained for the timeframes of one month and of one year. The best cost-effectiveness ratio (CER) was observed with oxybutynin IR for the urodynamic parameters. In terms of clinical parameters, oxybutynin IR and ER showed the best CER. Based on the key urological parameters analyzed, oxybutynin IR was considered the most cost-effective antimuscarinic agent.
A terapia antimuscarínica é vista como primeira escolha para o tratamento da hiperatividade detrusora de origem neurológica (HDON). No entanto, a maioria dos antimuscarínicos existentes é amplamente estudada em pacientes portadores de hiperatividade detrusora idiopática. Assim, existe escassez de pesquisas que avaliam esses fármacos na problemática da HDON, principalmente em termos de estudos de custo-efetividade. Diante isso, um estudo farmacoeconômico foi realizado (baseado no índice de preço máximo ao consumidor) para comparar os custos e a efetividade da oxibutinina e da tolterodina, em duas diferentes formulações, cápsulas de liberação imediata (LI) e controlada (LC), para o tratamento da HDON. Uma revisão sistemática da literatura foi conduzida para obtenção de dados urodinâmicos e clínicos relevantes (baseado em opinião de especialistas), quanto aos efeitos desses fármacos em pacientes com distúrbios urológicos de origem neurológica. Após essa etapa, um estudo farmacoeconômico foi conduzido e os custos envolvidos foram calculados sobre cada percentual de efetividade obtido, num horizonte temporal de 1 mês e 1 ano. A melhor razão de custo-efetividade (RCE) quanto aos parâmetros urodinâmicos foi obtida com uso de oxibutinina LI. Quantos aos parâmetros clínicos, oxibutinina LI e LC tiveram as melhores RCE. Baseando-se nos principais parâmetros urológicos analisados, oxibutinina LI foi considerada o antimuscarínico mais custo-efetivo.
Assuntos
Antagonistas Muscarínicos/análise , Bexiga Urinária Hiperativa/classificação , Tartarato de Tolterodina/análise , Bexiga Urinaria Neurogênica/classificação , Farmacoeconomia/estatística & dados numéricosRESUMO
A simple method has been developed for the simultaneous determination of N-butylscopolamine bromide and oxazepam in pharmaceutical formulations using first-order digital derivative spectrophotometry. Acetonitrile was selected as the solvent in which both compounds showed well-defined bands. Both analytes showed good stability in this solvent when solutions of the analytes were exposed to light and temperatures between 20 degrees and 80 degrees C. The simultaneous determination of both drugs was performed by the zero-crossing method at 226.0 and 257.0 nm for N-butylscopolamine and oxazepam, respectively. The linear range of determination was found to be 2.5 x 10(-7) to 8.0 x 10(-5) mol/L for N-butylscopolamine and 7.1 x 10(-8) to 8.0 x 10(-5) mol/L for oxazepam. A very good level of repeatability (relative standard deviation) of 0.2% was observed for N-butylscopolamine and oxazepam. The ingredients commonly found in pharmaceutical formulations do not interfere. The proposed method was applied to the determination of these drugs in pharmaceutical formulations (capsules).
Assuntos
Brometo de Butilescopolamônio/análise , Técnicas de Química Analítica/métodos , Química Farmacêutica/métodos , Oxazepam/análise , Espectrofotometria/métodos , Acetonitrilas/análise , Ansiolíticos/análise , Calibragem , Cápsulas , Química Farmacêutica/instrumentação , Estabilidade de Medicamentos , Etanol/análise , Luz , Metanol/análise , Modelos Químicos , Antagonistas Muscarínicos/análise , Reprodutibilidade dos Testes , Solventes , Comprimidos , Temperatura , Fatores de TempoRESUMO
En el músculo liso traqueal, los antagonistas muscarínicos (atropina) incrementan simultáneamente los niveles basales de los nucleóticos cíclicos (AMPc, GMPc), dependiendo del tiempo y dosis con máximo a 15 min y pEC50 7.4 mas o menos 0.2. El IBMX (10 µM), inhibidor no selectivo de PDEs, induce una respuesta similar. Sin embargo, la atropina potencial los incrementos del AMPc inducidos por 10 µM Rolipram (inhibidor PDE-IV) y los del GMPc producidos por µM Zaprinast (inhibidor PDE-V), sugiriendo la inhibición de una PDE que hidrolice ambos nucleótidos. La Vinpocetina (20 µM), inhibidor de PDE-Ic no dependiente de Calmodulina, produjo una respuesta semejante al antagonista muscarínic. Además, la atropia inhibió la PDE-Ic de las membranas celulares y no afectó la PDE-I cistosólca. Los antagonistas muscarínicos actúan como "agonistas inversos" sobre los m2/m3 AChR del sarcolema, iniciando una novedosa cascada que inhibe la PDE-Ic, provocando el incremento simultáneo del AMPc y GMPc en este tejido