تعیین نفوذپذیری داروهای کم محلول با استفاده از تکنیک single passintestinal perfusion در ژوژنوم موش صحرایی

Abstract

it is often desireed that new drug compounds are given orally beacause of the convenience of thisadministeraation route.However not all compound possess properties that are compatiable whit oral administration in fact there are several factors affecting absorption which their determination would be of great interest in predication of intestinal aborption of drugs.among these intestinal permeability is an important predictor.it reflects the ability of drug moleculles to cross the intestinal epithelial barrier.although human in vivo studies are the most desirable they seem difficult and time_consuming therefore several in vitro and in situ models have been developed for this purpose.male wistar rats were anaesthetized and single pass intestinal perfusion(SPIP)was performed in jejunal segment of small intestine at a flow rate of 0.2 ml of min.drug solution in PBS was entered into the segment and samples were taken from outlet tubing at different time points up to 90 min.then the samples were analyzed using HPLC_UV and effective permeability coefficinents(P eff)were calculated using recognizing formulation.the obtained mean P values were 6.2*10cms 2.0*10cms،1.1*10cms،3.3*10cms،2.0*10cms for carbamazepine،ibuprofen،ketoprofon،naproxen،furosemide and hydrochorothiazide respectively.the result of this study reveral that ratv jejunum P values correlated highly whit human P and the fraction absored after oral administration(R093) which indicates that it can be used whit precision to oral administration(R .98)Which indicates that it can be used whit precision to predict in vivo oral absorption in man.