马来酸海那替尼的大鼠在体肠吸收研究

Studies on rat intestinal absorption of Henatinib maleate in situ

目的:研究马来酸海那替尼大鼠在体肠吸收的情况。方法:采用大鼠在体肠单向灌流吸收实验模型,并应用重量法校正灌流液体积,HPLC法测定灌流液中药物浓度,进行了有无胆汁分泌、不同浓度、不同肠段的在体肠吸收试验。结果:结扎胆管组与不结扎胆管组吸收速率常数(Ka)分别为3.5×10-2、4.3×10-2/min,表观吸收系数(Papp)分别为3.0×10-3、3.1×10-3cm/min;在高、中、低3个浓度下的Ka分别为3.9×10-2、4.3×10-2、4.3×10-2/min,Papp分别为2.3×10-3、3.1×10-3、3.1×10-3cm/min;在十二指肠、空肠、回肠、结肠的Ka分别为4.5×10-2、3.7×10-2、4.2×10-2、4.1×10-2/min,Papp分别为3.3×10-3、2.8×10-3、3.0×10-3、3.5×10-3cm/min。结论:胆管结扎与否不影响药物的吸收;不同浓度对海那替尼在大鼠全肠道的吸收无显著影响,吸收机制为被动扩散;海那替尼在各肠段均吸收良好,没有特定吸收部位,适于制成口服吸收制剂。

AIM： To study the rat intestinal absorption of henatinib maleate in situ. METHODS： The rat single-pass intestinal perfusion technique was applied, and the gravimetry was used to correct the perfusion volume. The concentration of henatinib was determined by HPLC. A series of studies were carried out including the absorption under different bile secretion conditions, at different concentrations and at different intestinal regions. RESULTS： The drug absorp- tion rate constants （Ka） were 3.5×10^-2 ,4.3×10^-2/min, respectively, and the apparent absorption coeffi- cients （Papp） were 3.0×10^-3,3.1×10^-3cm/min, respectively, in the groups of bile duct ligation and without bile duct ligation. Moreover, K, were 3.9 ×10^-2,4.3 ×10^-2,4.3 ×10^-2/min, respectively, and Papp were 2.3×10^-3, 3.1 ×10^-3, 3.1 ×10^-3 cm/min, respectively, at three perfusate drug concentrations of high, middle and low levels. And Ka were 4.5×10^-2 ,3.7 ×10^-2 ,4.2×10^-2,4.1×10^-2/min, respectively, and Papp were 3.3×10^-3 ,2.8×10^-3, 3.0 ×10^-3, 3.5 ×10^-3cm/min, respectively, on the duodenum, jejunum, ileum and colon. CONCLUSION： The absorption of henatinib is not apparently influenced by bile seeretion. Concentration of henatinib has no significant effect on its absorption in all segments of rat intestine. The absorption is consistent with passive transportation. Henatinib is well absorbed in every segment of the intestine and has no specific absorption site. So, henatinib can be made into oral dosage forms.