Abstract
In an attempt to develop a suitable dosage form of systemically acting drugs for pulmonary administration, the absorption of xanthine derivatives from the lung of rats was studied. The pulmonary absorption of xanthine derivatives was rapid, and these drugs were transferred into the circulation. For example, in the case of theophylline (500 μg/rat), the absorption within 1 min was about 90%, and in the cases of aminophylline (500 μg/rat) and caffeine (1000 μg/rat), 96% and 97%, respectively. The maximum plasma levels in all cases were achieved within 30 s. The pulmonary absorption of these drugs was not affected by body weight or wet weight of lung. When the dose of these drugs was raised 10- to 15-fold, the amount of compound absorbed was directly proportional to the dose, the percentage absorption remaining constant. The pulmonary absorption of these drugs was not significantly different at pH between 6.4 and 8.4, but at pH 9.4, the absorption of theophylline and aminophylline was significantly decreased (p<0.001), though the absorption of caffeine remained nearly constant. Comparison of the partition coefficients of these drugs indicated that the pulmonary absorption of xanthine derivatives depends on lipid solubility. The pulmonary absorption of theophylline was unaffected by changes of the osmotic pressure of drug solutions. These results suggest that the pulmonary absorption of xanthine derivatives can indeed occur very rapidly, and that the lung may afford a favorable route of administration to obtain a systemic effect of drugs.
