Sagara K, Yamada I, Kawazoe Y, Mizuta H, Shibata M
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Biol Pharm Bull. 1994 Jan;17(1):117-20. doi: 10.1248/bpb.17.117.
The gastrointestinal (GI) physiology of beagle dogs was effectively regulated with a combined treatment using intramuscular pentagastrin (10 micrograms/kg x 2) and intravenous atropine sulfate (0.02 mg/kg x 1). The superiority of the GI physiology regulated-dogs over the intact dogs was confirmed by comparative bioavailability studies using two classes of preparations of poorly water-soluble 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H- thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180). Both the fine granules and the tablets of Y-24180 exhibited similar absorption profiles in the intact dogs, whereas the latter preparations revealed a delayed plasma curve of the drug in the regulated-dogs. The absorption profiles of the two classes of Y-24180 preparations in the regulated-dogs simulated those in healthy volunteers. The combined-treatment of beagle dogs with pentagastrin and atropine sulfate was suggested to supply a useful animal model for predicting the absorption characteristics of poorly water-soluble drugs and their preparations in humans.
通过肌肉注射五肽胃泌素（10微克/千克×2）和静脉注射硫酸阿托品（0.02毫克/千克×1）的联合治疗，有效调节了比格犬的胃肠（GI）生理功能。使用两类难溶性4-（2-氯苯基）-2-[2-（4-异丁基苯基）乙基]-6,9-二甲基-6H-噻吩并[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂卓（Y-24180）制剂进行的比较生物利用度研究证实了胃肠生理功能得到调节的犬类比未处理犬具有优势。Y-24180的细颗粒剂和片剂在未处理犬中表现出相似的吸收曲线，而后者制剂在胃肠功能调节犬中显示出药物血浆曲线延迟。两类Y-24180制剂在胃肠功能调节犬中的吸收曲线与健康志愿者相似。五肽胃泌素和硫酸阿托品联合治疗比格犬被认为可提供一个有用的动物模型，用于预测难溶性药物及其制剂在人体内的吸收特性。
