Pretorius Erina, Bouic Patrick J D
Medical Microbiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
AAPS PharmSciTech. 2009;10(1):270-5. doi: 10.1208/s12249-009-9207-4. Epub 2009 Mar 12.
The pharmaceutical industry is in need of rapid and accurate methods to screen new drug leads for intestinal permeability potential in the early stages of drug discovery. Excised human jejunal mucosa was used to investigate the permeability of the small intestine to four oral drugs, using a flow-through diffusion system. The four drugs were selected as representative model compounds of drug classes 1 and 3 according to the biopharmaceutics classification system (BCS). The drugs selected were zidovudine, propranolol HCl, didanosine, and enalapril maleate. Permeability values from our in vitro diffusion model were compared with the BCS permeability classification and in vivo and in vitro gastrointestinal drug permeability. The flux rates of the four drugs were influenced by the length of the experiment. Both class 1 drugs showed a significantly higher mean flux rate between 2 and 6 h across the jejunal mucosa compared to the class 3 drugs. The results are therefore in line with the drugs' BCS classification. The results of this study show that the permeability values of jejunal mucosa obtained with the flow-through diffusion system are good predictors of the selected BCS class 1 and 3 drugs' permeation, and it concurred with other in vitro and in vivo studies.
制药行业需要快速准确的方法，以便在药物研发的早期阶段筛选具有肠道渗透潜力的新药先导化合物。使用流通扩散系统，采用切除的人空肠黏膜来研究小肠对四种口服药物的渗透性。根据生物药剂学分类系统（BCS），选择这四种药物作为第1类和第3类药物的代表性模型化合物。所选药物为齐多夫定、盐酸普萘洛尔、去羟肌苷和马来酸依那普利。将我们体外扩散模型得到的渗透性值与BCS渗透性分类以及体内和体外胃肠道药物渗透性进行比较。四种药物的通量率受实验时长的影响。与第3类药物相比，两种第1类药物在2至6小时内穿过空肠黏膜的平均通量率显著更高。因此，结果与药物的BCS分类一致。本研究结果表明，通过流通扩散系统获得的空肠黏膜渗透性值是所选BCS第1类和第3类药物渗透的良好预测指标，并且与其他体外和体内研究结果一致。
