In vitro and in vivo deconvolution assessment of drug release kinetics from oxprenolol Oros preparations.

Abstract

The relationship between in vitro and in vivo drug release from Oros systems has been examined by analysing plasma concentration data from two pharmacokinetic studies, using a numerical deconvolution technique. This method generates an input profile by comparing the response with that achieved following an instantaneous reference unit dose. The approach is conceptually simple and does not require compartmental pharmacokinetic modelling or curve fitting. In the analysis of the first study, the plasma profile following intravenous dosing was used as the reference function, allowing the combined release/absorption process to be calculated; for the second, an oral bolus was used, the result of the deconvolution therefore indicating the in vivo dissolution rate of the Oros systems. The in vivo release from Oros in most volunteers followed the same pattern as that measured in vitro; only after 6‐8 h was the decline in the in vivo release rate somewhat greater than expected. In a few individuals the cumulative absorption profile reached an early plateau level which coincided, on some but not all occasions, with the premature excretion of the Oros system from the body. The amount of drug in recovered systems agreed reasonably with the prediction of the deconvolution analysis. 1985 The British Pharmacological Society