Hydrogen peroxide-induced epithelial damage increases terbutaline transport in guinea-pig tracheal wall: Implications for drug delivery

An isolated vagus nerve-tracheal tube preparation from guinea-pig was treated intraluminally with hydrogen peroxide (H₂O₂) at various concentrations. Exposure to, 100 mmol/L H₂O₂ for 20 min was chosen for further experiments since it appeared to cause selective damage to the epithelium. Thus the subepithelial layers of the tracheal wall appeared intact as judged by light microscopic examination. The response to nerve stimulation (increase in intratracheal pressure) was attenuated by only about 20%. Terbutaline administered into the tracheal lumen caused a concentration-dependent inhibition of the response to nerve stimulation. In tracheal preparations pretreated with 100 mmol/L H₂O₂ there was a 20-fold decrease in the EC₅₀ for terbutaline. The EC₅₀ for terbutaline added to the external medium was not changed by the H₂O₂ pretreatment. The efflux of ³H-terbutaline from the tracheal lumen into the external medium was three times higher in H₂O₂-treated than in control preparations. It is concluded that in the H₂O₂-damaged epithelium the absorption of terbutaline is enhanced resulting in a better availability of the drug in the smooth muscle layer after intraluminal administration.