Martin G P, Loveday B E, Marriott C
Dept. of Pharmacy, Brighton Polytechnic, UK.
Eur Respir J. 1990 Apr;3(4):392-6.
Mucus was collected daily from open-ended pouches established surgically in three mini-pigs. After a five day control period bromhexine hydrochloride (BHCl) was administered to each pig at dose levels of 0.5, 1.0 and 2.0 mg.kg-1 twice daily for five days. Each study period was followed by a five day washout period, when mucus was collected but no drug given. The viscoelastic properties of each mucus sample were determined using creep compliance analysis. BHCl was shown to reduce the residual shear viscosity (p less than 0.05) and increase the instantaneous shear compliance at all dose levels (p less than 0.005), despite the large inherent intra- and inter-animal variation in the rheological properties of the daily samples. No change was found in the wet weight of the mucus samples throughout any of the study periods. This experimental model would appear to provide a valuable in vivo method of assessing the mucoregulatory potential of administered compounds.
每天从三只小型猪手术建立的开口袋中收集黏液。在为期五天的对照期后,以0.5、1.0和2.0 mg·kg⁻¹的剂量水平,每天给每只猪服用两次盐酸溴己新(BHCl),持续五天。每个研究期之后是为期五天的洗脱期,在此期间收集黏液但不给予药物。使用蠕变柔量分析确定每个黏液样本的粘弹性特性。尽管每日样本的流变特性在动物体内和动物间存在很大的固有差异,但BHCl在所有剂量水平下均显示出降低残余剪切粘度(p<0.05)并增加瞬时剪切柔量(p<0.005)。在任何研究期内,黏液样本的湿重均未发现变化。该实验模型似乎提供了一种评估给药化合物黏液调节潜力的有价值的体内方法。