Modeling the heterogeneous intestinal absorption of propiverine extended-release.
2015
Abstract Propiverine is a widely used antimuscarinic drug with bioavailability that is limited by intestinal first-pass extraction. To study the apparent heterogeneity in intestinal first-pass extraction, we performed a population analysis of oral concentration–time data measured after administration of an extended-release formulation of propiverine in ten healthy subjects. Using an inverse Gaussian function as input model, the assumption that the systemically available fraction increases as a sigmoidal function of time considerably improved the fit. The step-like increase in this fraction at time t = 3.7 h predicted by the model suggests that propiverine is predominantly absorbed in colon. A nearly perfect correlation was found between the estimates of bioavailability and mean dissolution time.
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