Hochhaus G, Gonzalez-Rothi R J, Lukyanov A, Derendorf H, Schreier H, Dalla Costa T
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
Pharm Res. 1995 Jan;12(1):134-7. doi: 10.1023/a:1016259225244.
Triamcinolone acetonide (TA, 22 micrograms) was given to rats by intravenous (i.v.) injection or intratracheal (IT) instillation. Free glucocorticoid receptors were monitored over time in liver and lung using an ex-vivo receptor binding technique. After i.v. administration of a TA solution, the reduction of free receptors over time was very similar in lung and liver (AUCLung = 280 +/- 47% h; AUCLiver = 320 +/- 76% h). Intratracheal instillation of the same solution produced time profiles which mirrored those of i.v. injection (AUCLung = 260 +/- 41% h; AUCLiver = 330 +/- 50% h). The lack of lung targeting was also reflected in the failure to show any significant difference in the pulmonary targeting factor T (AUCLung/AUCLiver) between i.v. (T = 0.84 +/- 0.18) and IT (T = 0.78 +/- 0.03) administration. In contrast, a certain degree of lung specificity was observed after IT instillation of a glucocorticoid suspension (22 micrograms; AUCLung = 160 +/- 135% h; AUCLiver = 65 +/- 91% h, T = 2.3 +/- 0.5) as indicated by significant differences in T between i.v. injection and IT instillation (p = 0.038). The method presented provides a means of simultaneously assessing pulmonary and systemic effects after different forms and routes of administration and might be of value in further studying multiple aspects of inhalation glucocorticoid therapy.
将曲安奈德（TA，22微克）通过静脉注射（i.v.）或气管内（IT）滴注给予大鼠。使用离体受体结合技术随时间监测肝脏和肺中游离糖皮质激素受体。静脉注射TA溶液后，肺和肝脏中游离受体随时间的减少非常相似（肺的曲线下面积AUCLung = 280±47% h；肝脏的曲线下面积AUCLiver = 320±76% h）。气管内滴注相同溶液产生的时间曲线与静脉注射的相似（AUCLung = 260±41% h；AUCLiver = 330±50% h）。肺靶向性的缺乏也反映在静脉注射（T = 0.84±0.18）和气管内滴注（T = 0.78±0.03）之间的肺靶向因子T（AUCLung/AUCLiver）没有显著差异。相比之下，气管内滴注糖皮质激素混悬液（22微克；AUCLung = 160±135% h；AUCLiver = 65±91% h，T = 2.3±0.5）后观察到一定程度的肺特异性，这由静脉注射和气管内滴注之间T的显著差异表明（p = 0.038）。所提出的方法提供了一种同时评估不同给药形式和途径后肺部和全身效应的手段，可能对进一步研究吸入性糖皮质激素治疗的多个方面有价值。
