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本研究采用大鼠小肠在体单向(single-pass)灌流模型,收集灌流后不同时间点灌流液和肠系膜静脉血,应用GC-MS联用法测定灌注液和血浆中的布格呋喃含量,并计算布格呋喃渗透系数[Plumen=-(Q/2πrl)Ln(Cout/Cin)和Pblood=(ΔMB/Δt)/(2πrl)],从而反映布格呋喃的代谢变化。同时,观察CYP3A选择性抑制剂醋竹桃霉素(TAO)、CYP3A和P-糖蛋白(P-gp)共同抑制剂环孢素A(CsA)和P-gp选择性抑制剂LSN335984对布格呋喃自大鼠肠道吸收的影响。结果表明,在大鼠小肠在体单向灌流模型中加入LSN335984、TAO和CsA后,大鼠肠系膜静脉血中布格呋喃的累积量分别为73.4、82.9和98.3pmol·cm-2,与对照组比较分别增加3.9倍、4.6倍和5.6倍,代谢分别减少12%、11%和21%。提示CYP3A和P-gp选择性抑制剂可明显减少布格呋喃在大鼠肠道的首过效应,促进布格呋喃的肠道吸收。由此可见,P-gp与CYP3A两者联合作用是引起布格呋喃口服生物利用度低的重要因素,两者对布格呋喃小肠吸收均具有重要影响。
In this study, single-pass perfusion model was used in rat small intestine to collect perfusate and mesenteric venous blood at different time points after perfusion. The content of bufurine in perfusate and plasma was determined by GC-MS The buzafur permeation coefficient [Plumen = - (Q / 2πrl) Ln (Cout / Cin) and Pblood = (ΔMB / Δt) / (2πrl )] was calculated to reflect the metabolic changes of buforfuran. In the meantime, the effects of CYP3A selective inhibitor vinegoamycin (TAO), CYP3A and P-glycoprotein (CsA) and P-gp selective inhibitor LSN335984 Effects of Furan on Intestinal Absorption in Rats. The results showed that after the addition of LSN335984, TAO and CsA into the rat intestinal small intestine, the cumulant budesonide concentrations in rat mesenteric venous blood were 73.4, 82.9 and 98.3 pmol · cm-2, respectively. Compared with the control group Compared with 3.9 times, 4.6 times and 5.6 times respectively, the metabolism decreased by 12%, 11% and 21% respectively. Tip CYP3A and P-gp selective inhibitors can significantly reduce the first pass effect of buagfuran in the intestine of rats and promote the intestinal absorption of bufogenin. Thus, the combined effect of both P-gp and CYP3A is an important factor in the oral bioavailability of buagafuran, both of which have an important impact on the intestinal absorption of buagfuran.