Role of concentration-dependent plasma protein binding in disopyramide disposition

摘要: Plasma disopyramide concentration-time data and plasma protein binding measurements were obtained in 12 patients requiring for suppression of their cardiac arrhythmias. The fraction unbound to proteins varies from approximately 0.19 0.46 over the therapeutic range total concentrations (2–8 mg/liter). Data single multiple intravenous doses analyzed using two models based on hypothesis either that clearance is independent concentration (total model) or (free model). This analysis indicates only free model satisfactorily describes as a linear system. Using doses, infusions designed each patient which would rapidly attain maintain predetermined concentrations. calculated observed close agreement. In studied, at any given concentration, there was an twofold proteins. Mean are therefore little value predicting concentration. Difficulties clinical management receiving disopyramide, resulting nonlinear disposition usually measured concentrations, discussed.