Studies on the factors affecting pulmonary absorption of xanthine derivatives in the rat.
Studies on the factors affecting pulmonary absorption of xanthine derivatives in the rat.
复制标题
影响黄嘌呤衍生物大鼠肺吸收因素的研究
DOI：
10.1248/cpb.35.2038
复制
发表时间：
1987
影响因子：
1.7
通讯作者：
S. Kitazawa
中科院分区：
文献类型：
--
作者：
E. Arakawa;S. Kitazawa
在尝试开发用于肺部给药的全身作用药物的合适剂型中，研究了黄嘌呤衍生物从大鼠肺中的吸收。黄嘌呤衍生物的肺部吸收迅速，这些药物被转移到循环中。例如，在茶碱（500 μg/大鼠）的情况下，1分钟内的吸收约为90%，而在氨茶碱（500 μg/大鼠）和咖啡因（1000 μg/大鼠）的情况下，分别为96%和97%。所有病例的最大血浆水平均在30 s内达到。这些药物的肺吸收不受体重和肺湿重的影响。当这些药物的剂量增加10- 15倍时，化合物的吸收量与剂量成正比，吸收百分比保持不变。在pH 6.4和8.4之间，这些药物的肺吸收没有显著差异，但在pH 9.4时，茶碱和氨茶碱的吸收显著降低（p<0.001），而咖啡因的吸收几乎保持不变。这些药物的分配系数的比较表明，肺吸收的黄嘌呤衍生物取决于脂溶性。茶碱的肺吸收不受药物溶液渗透压变化的影响。这些结果表明，黄嘌呤衍生物的肺部吸收确实可以非常迅速地发生，并且肺部可以提供有利的给药途径以获得药物的全身效应。
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.