RESUMO
An enantioselective method using liquid-phase microextraction (LPME) followed by HPLC analysis was developed for the determination of oxybutynin (OXY) and its major metabolite N-desethyloxybutynin (DEO) in rat liver microsomal fraction. The LPME procedure was optimized using multifactorial experiments. Under the optimal extraction conditions, the mean recoveries were 61 and 55% for (R)-OXY and (S)-OXY, respectively, and 70 and 76% for (R)-DEO and (S)-DEO, respectively. The validated method was employed to an in vitro biotransformation study using rat liver microsomal fraction. The results demonstrated the enantioselective biotransformation of OXY.
Assuntos
Ácidos Mandélicos/análise , Animais , Biotransformação , Fracionamento Químico/métodos , Masculino , Ácidos Mandélicos/farmacocinética , Microssomos Hepáticos/metabolismo , Ratos , Ratos Wistar , EstereoisomerismoRESUMO
Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and incontinence, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing side effects (e.g., dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin (N-DEO) is produced and this compound is deemed to be responsible for anticholinergic side effects such as dry mouth. This novel oxybutynin formulation offers patients with OAB and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.
Assuntos
Ácidos Mandélicos/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Bexiga Urinária Hiperativa/tratamento farmacológico , Administração Cutânea , Ensaios Clínicos como Assunto , Sistemas de Liberação de Medicamentos , Humanos , Ácidos Mandélicos/farmacocinética , Antagonistas Muscarínicos/farmacocinéticaRESUMO
Overactive bladder is commonly treated with oral anticholinergic drugs such as oxybutynin chloride. Although oral anticholinergic agents have been effective in controlling urinary urgency and incontinence, adverse events, particularly dry mouth, often cause patients to discontinue oral therapy and to endure incontinence. Oxybutynin can be delivered transcutaneously, maintaining the efficacy of oral oxybutynin while significantly minimizing side effects (e.g., dry mouth) that may complicate therapy. By avoiding hepatic and gastrointestinal metabolism of oxybutynin, less N-desethyloxybutynin (N-DEO) is produced and this compound is deemed to be responsible for anticholinergic side effects such as dry mouth. This novel oxybutynin formulation offers patients with OAB and urge urinary incontinence a well-tolerated option for managing the symptoms of overactive bladder.