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缺氧和高碳酸血症对家兔沙丁胺醇动力学及低钾血症效应的影响

Influence of hypoxia and hypercapnia on the kinetics and hypokaliaemic effect of salbutamol in the rabbit.

作者信息

Perreault S, Saunier C, Ong H, Du Souich P

机构信息

Département de Pharmacologie, Université de Montréal, Québec, Canada.

出版信息

Xenobiotica. 1995 Mar;25(3):271-81. doi: 10.3109/00498259509061851.

Abstract
  1. The aims were to document the influence of moderate hypoxia or hypercapnia on salbutamol kinetics and its hypokaliaemic effect, following its administration through the intravenous (60 micrograms/kg), intratracheal (60 micrograms/kg), and oral (2400 micrograms/kg) routes (n = 5). In control animals, PaO2 was around 85 mmHg and PaCO2 20 mmHg; in hypoxic animals PaO2 was around 40 mmHg and in the hypercapnic rabbit PaCO2 was 50 mmHg. 2. Following the intravenous administration of salbutamol, the apparent volume of distribution increased two-fold (p < 0.05) in animals with hypoxia and hypercapnia. Consequently, its half life was enhanced (p < 0.05). Given via the trachea, salbutamol bioavailability was decreased by hypoxia. 3. When salbutamol was given orally, hypoxia or hypercapnia increased the area under salbutamol plasma concentration as a function of time (p < 0.05). 4. In control animals, the salbutamol hypokaliaemic effect was greater when administered orally than through the other routes. Compared with control animals, the experimental conditions reduced the hypokaliaemic effect of salbutamol only when given orally. 5. It is concluded that salbutamol kinetics and dynamics can be altered by hypoxia and hypercapnia.
摘要
  1. 目的是记录中度缺氧或高碳酸血症对沙丁胺醇动力学及其低钾血症效应的影响,通过静脉注射(60微克/千克)、气管内注射(60微克/千克)和口服(2400微克/千克)给药途径(n = 5)。在对照动物中,动脉血氧分压(PaO2)约为85 mmHg,动脉血二氧化碳分压(PaCO2)为20 mmHg;在缺氧动物中,PaO2约为40 mmHg,在高碳酸血症兔中,PaCO2为50 mmHg。2. 静脉注射沙丁胺醇后,缺氧和高碳酸血症动物的表观分布容积增加了两倍(p < 0.05)。因此,其半衰期延长(p < 0.05)。通过气管给药时,缺氧会降低沙丁胺醇的生物利用度。3. 口服沙丁胺醇时,缺氧或高碳酸血症会增加沙丁胺醇血浆浓度随时间变化的曲线下面积(p < 0.05)。4. 在对照动物中,口服沙丁胺醇时的低钾血症效应比通过其他途径给药时更大。与对照动物相比,实验条件仅在口服给药时降低了沙丁胺醇的低钾血症效应。5. 结论是缺氧和高碳酸血症可改变沙丁胺醇的动力学和动态变化。

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