Percutaneous absorption of pindolol and pharmacokinetic analysis of the plasma concentration.

Abstract

The percutaneous (p.c.) absorption of pindolol, a beta-blocker, through rabbit skin was examined by in vitro and in vivo studies. Additionally, for practical use of the transdermal system (TTS), a trial for sustaining a suitable plasma concentration of pindolol by using a rate-controlling membrane and for describing plasma drug levels after p.c. application by using a simple pharmacokinetic model was tested. As a result, the drug penetrated through rabbit skin in vitro at a zero-order rate. In vivo, the drug was also absorbed through the skin from a gel base with or without enhancers. The gel preparation with Azone (Rp. 2) gave high plasma levels of pindolol. The transdermal system produced with Rp. 2 and a rate-controlling membrane (Hipore 4050) provided relatively constant plasma levels for 48 h. The model presented could describe the time course of plasma pindolol concentrations following p.c. application of the systems.