The Absorption Of SU2237

Purpose: To study the absorption of SU2237in situ and optimize the extract oflecithin from egg. Then use the lecithin to simulate artificial membrane permeabilityassay（AMPA）and evaluate if the AMPA can predict the permeability of drugs in vivo.Method: we employed a simple method single-pass intestinal perfusiontechnique （SPIP） performed in rats to evaluate experimentally intestinal permeabilityof SU2237and the fraction absorbed of different doses and different pHs in threesegments of intestinal. An UV method was developed to determine the sample ofperfusate. All the requirement of pharmacopoeia including specificity, standard curve,recovery, accuracy and stability meet the standard. SPIP was performed in rat’s threeisolated intestinal segments （duodenum, jejunum, and ileum） at the sameconcentration of SU2237（200μg/mL） to test whether the intestinal transport ofSU2237exhibited site-dependent changes, and the rat’s whole intestines was appliedto assess the permeability of three different concentrations of SU2237（50,200,800μg/mL） to investigate whether the intestinal transport of SU2237exhibitedconcentration-dependent changes. Besides, three perfusions of different pHs （pH5.4,pH6.8, pH7.4） were perfused with SU2237（200μg/mL） in the rat’s whole intestines tofind out whether the intestinal absorption of SU2237was affected by pH variation.The solvent extraction method was used to extract the lecithin in egg. Theaffecting factors were investigated by single factor and the orthogonal design wasused to optimizing extraction conditions.According to the principle of PAMPA, we would design a simple device usingthe lecithin to predict the pearmeability of drugs. Results: Applying the mentioned validated UV method, we successfullydetermined the level of SU2237following intestinal perfusion in rats. Effectivepermeability coefficient （Peff） of SU2237（200μg/ml） in duodenum group found to be（18.41±1.32）*10^-5cm s^-1and was significantly different from the jejunum and theileum groups which was7.4784±0.6350*10^-5cm s^-1and （7.47±0.82）*10^-5cm s^-1,respectively （P=0.005）. Besides, the pH dependent experiences showed that the valueof Peffat pH5.4and pH6.8were6.9909±1.2834*10^-5cm s^-1and7.8623±1.2868*10^-5cm s^-1respectively which were significantly lower than thepH7.4(12.3212±1.1595*10^-5cm s^-1) at200μg/mL in the whole intestinal （P<0.05）.Furthermore, Peffvalue of SU2237in the whole intestinal at high concentration800μg/ml was found to be6.64±1.85*10^-5cm s^-1and was significantly lower thanthose at low and medium concentrations （50and200μg/mL） which was12.32±1.16*10^-5cm s^-1,13.26±2.47*10^-5cm s^-1respectively （P<0.05）.The optimization result of extracting lecithin from egg was: The extraction mixingtime is40min and the extraction temperature is25℃. What is more, the ratiobetween solvent and solute was6ml/g and the extraction yield can be8%or so andthe phosphorus content was detected to be11.65%by digestion and phosphorusmethod following the extraction condition above. The apparent permeability （Peff） ofibuprofen simulated by AMPA was （6.7348±1.3514）*10^-6cm/s and the SU2237was （5.0168±0.3905）*10^-6cm/s.Conclusion: Intestinal permeability of SU2237is concentration-and site-dependent. Intestinal absorption of SU2237may be via passive and transcelluarmechanism involving an active, saturable process, or via a membrane transportprotein in the gut wall, especially in the duodenum. The Peffvalues of different part ofintestinal, pHs and concentration are larger than10^-6cm/s indicated that SU2237is ahigh permeability drug.The apparent permeability （Peff） of ibuprofen simulated by AMPA was （6.7348±1.3514）*10^-6cm/s which was in the same order of magnitude with PAMPA and theSU2237was （5.0168±0.3905）*10^-6cm/s.