Distribution studies of theophylline: microdialysis in rat and horse and whole body autoradiography in rat

After intravenous administration of theophylline, microdialysis has been used for studying the non protein bound theophylline concentration in blood and in lung tissue in the rat as well as in two horses. The distribution pattern of 14C-theophylline in the rat was also investigated. When the distribution of theophylline was completed the time course of free drug in the interstitial fluid in lung tissue was in good agreement with the total concentration-time profile in plasma in both species. In the rat the free concentration of theophylline in the lung was slightly lower than the free concentration in the blood from 40 to 300 min. The in vivo protein binding in blood was 48.8 +/- 6.2% in the rats (n = 9) and 8-25% in the horses (n = 2). The whole body autoradiography study in rat showed that the concentration of radioactivity in the lung followed the blood concentration very closely up to 24 h after injection. The effect of theophylline in the lung can be assumed to be related to the plasma concentration of theophylline, since the concentration-time profile in plasma reflects the time course in the lung.