Formulation Technology Research Laboratories, Daiichi Sankyo Co., Ltd., Hiratsuka, Kanagawa, Japan.
Eur J Pharm Biopharm. 2010 Jun;75(2):238-44. doi: 10.1016/j.ejpb.2010.03.009. Epub 2010 Mar 21.
The purpose of this study was to develop a new method using beagle dogs in order to evaluate the colonic absorption properties of oral extended-release (ER) solid dosage forms. The established method is not only noninvasive and inexpensive but full-sized ER dosage forms are also directly administered to the colons of conscious dogs through the anus with an endoscope and modified bioptome. In the method, it was possible to administer the ER dosage forms into the ascending colon of dogs within 30 s-1 min. The colonic absorption of Voltaren-XR (Diclofenac sodium), Glucophage-XR (metformin), Pacif (morphine hydrochloride), Herbesser-R (diltiazem hydrochloride) and Plendil (felodipine), which are currently on the market, were investigated by this method. The relative bioavailabilities of these ER dosage forms to oral drug solution were 100.3%, 42.5%, 60.6%, 46.3% and 29.8%, respectively. Some of these results reflected the human colonic absorption profiles reported in the literature. This newly developed method could provide researchers with an alternative way to predict the human colon absorption performance of oral ER delivery systems.
本研究旨在开发一种新方法,使用比格犬来评估口服延长释放(ER)固体制剂的结肠吸收特性。所建立的方法不仅是非侵入性和廉价的,而且还可以通过内窥镜和改良的活检钳将全尺寸的 ER 剂型直接施用于清醒犬的结肠。在该方法中,有可能在 30 秒至 1 分钟内将 ER 剂型施用到犬的升结肠中。通过该方法研究了目前市场上的 Voltaren-XR(双氯芬酸钠)、Glucophage-XR(二甲双胍)、Pacif(盐酸吗啡)、Herbesser-R(盐酸地尔硫卓)和 Plendil(非洛地平)等 ER 剂型的结肠吸收情况。这些 ER 剂型相对于口服药物溶液的相对生物利用度分别为 100.3%、42.5%、60.6%、46.3%和 29.8%。其中一些结果反映了文献中报道的人类结肠吸收特征。这种新开发的方法可以为研究人员提供一种替代方法来预测口服 ER 给药系统的人体结肠吸收性能。