Pharmacokinetic investigation of the absorption of oxprenolol from Oros delivery systems in healthy volunteers: comparison of in vivo and in vitro drug release.

Abstract

The absorption kinetics of oxprenolol have been investigated in eight healthy volunteers after single dosing with 16/260 Oros drug delivery systems. Oxprenolol disposition kinetics in individual subjects were estimated from intravenous dose data. Loo-Riegelman analysis of the plasma concentration data indicated an extended duration of drug absorption for the Oros system. Initially, the in vivo absorption rate was similar to the in vitro release rate but after 5-6 h it slowed perceptibly. However, at later times similar in vivo and in vitro rates were again observed. The absolute bioavailabilities for prototype and clinical trial systems were shown to be similar, at approximately 42%, and no significant differences in plasma profiles or pharmacokinetic constants were detected between the two Oros forms. A comparison of plasma concentration data in seven subjects who received the prototype system on two occasions in separate studies indicated a consistent level of drug absorption from this preparation. Approximately 10-15% of the administered dose was found in Oros systems recovered from faeces. The quantity of drug remaining was poorly correlated with the observed areas under the plasma concentration-time curve.