摘要
目的:观察复方黄甘颗粒对P-糖蛋白(P-gp)底物罗丹明123(R123)和非P-gp底物6-羧基荧光素(CF)经肠黏膜转运的影响,为复方黄甘颗粒与P-gp底物药物合理联用提供依据。方法:20只SPF级SD雄性大鼠,体重(250±20)g,用随机数字表法分为生理盐水组和复方黄甘颗粒组,每组10只。分别给予生理盐水20mL/kg和1.0g/L复方黄甘颗粒溶液20mL/kg灌胃,2次/d,连续7d。1周后大鼠禁食16～18h,用10%水合氯醛(3mL/kg)腹腔麻醉,取空肠标本3～4cm,用体外扩散池法检测2组大鼠空肠黏膜对R123和CF透过性的影响,比较2组吸收方向转运[黏膜侧(M)-浆膜侧(S)]和分泌方向转运(S-M)的表观渗透系数(Papp)及泵出比(ER)。结果:生理盐水组与复方黄甘组R123吸收方向的Papp分别为(3.54±0.86)×10-6和(2.39±0.44)×10-6cm/s,分泌方向的Papp分别为(8.68±3.76)×10-6和(8.34±2.47)×10-6cm/s;生理盐水组与复方黄甘组CF吸收方向的Papp分别为(5.40±3.20)×10-6cm/s和(3.28±1.41)×10-6cm/s,分泌方向的Papp分别为(5.09±1.71)×10-6cm/s和(3.98±1.02)×10-6cm/s;差异均无统计学意义(均P>0.05)。生理盐水组R123的ER为2.45,CF的ER为0.94;复方黄甘组R123的ER为3.50,CF的ER为1.21。结论:复方黄甘颗粒对肠黏膜P-gp的活性无明显影响,提示复方黄甘颗粒与R123类似的P-gp底物药物联合应用较为安全。
Objective：To observe the effects of compound Huanggan granules（CHG）on the intestinal mucosa transport of a P-glycoprotein substrate rhodamine 123（R123）and a non-P-glycoprotein substrate 6-carboxyfluorescein（CF）in order to provide the evidence of rational use of the combination of CHG and a P-glycoprotein substrate drug.Methods：Twenty SPF SD male rats,weighing（250±20）g,were divided into the normal saline（NS）group and the CHG group by random-digit table method（n=10,in each group）.The rats in the NS and CHG groups were gavaged with normal saline solution（20 mL/kg）and 1.0 g/L CHG solution（20 mL/kg）twice daily for 7 days,respectively.One week later,the rats were fasted for 16-18 hours and anesthetized with 10% chloral hydrate（3 mL/kg,IP）,and a 3-4 cm segment of jejunum of each rat was obtained.The effects of rat jejunum mucosa in both groups on the permeability of R123 and CF were measured by ussing chamber method in vitro.The apparent permeability coefficient（Papp）of absorptive（mucosal to serosal）and secretary（serosal to mucosal）transport direction of R123 and CF as well as the efflux ratios（ER）were compared between the two groups.Results：The Papp of R123 in the absorptive direction in the NS and CHG groups was（3.54±0.86）×10-6 cm/s and（2.39±0.44）×10-6 cm/s,respectively,and the Papp of R123 in the secretory direction was（8.68±3.76）×10-6 cm/s and（8.34±2.47）×10-6 cm/s,respectively.The Papp of CF in the absorptive direction in the NS and CHG groups was（5.40±3.20）×10-6 cm/s and（3.28±1.41）×10-6 cm/s,respectively,and the Papp of CF in the secretory direction was（5.09±1.71）×10-6 cm/s and（3.98±1.02）×10-6 cm/s,respectively.There was no statistically significant difference（all P0.05）.The ER of R123 and CF in the NS group were 2.45 and 0.94,the ER of R123 and CF in the CHG group were 3.50 and 1.21,respectively.Conclusion：The compound Huanggan granules have no marked effect on P-glycoprotein activity in the intestinal mucosa.It is suggested that the combination therapy with CHG and a P-glycoprotein substrate drug which is similar to rhodamine 123 is relatively safe.
出处
《药物不良反应杂志》
2010年第5期313-316,共4页
Adverse Drug Reactions Journal
基金
广东省科技计划项目(2010B030700014)
广州白云区科技计划资助项目(2009-SZ-36)
关键词
复方黄甘颗粒
P-糖蛋白
扩散池
透过性
compound Huanggan granules
P-glycoprotein substrate
ussing chamber
permeability
