地塞米松羧甲基魔芋胶小丸的大鼠体内释药探讨

目的研究地塞米松羧甲基魔芋胶小丸体内释药情况,评价其结肠定位释药特性。方法以地塞米松羧甲基纤维素钠混悬液为对照,将地塞米松羧甲基魔芋胶小丸大鼠灌胃给药(以地塞米松量计,给药剂量为10mg/kg),采用HPLC法测定大鼠体内血药浓度经时变化和粪便排泄物中药物量经时变化,计算制剂在结肠内容物的相对靶向释药指数。结果与对照组相比,小丸组血药浓度存在1h时滞,Tmax由4h延至8h,Cmax由(6.46±0.92)mg/L明显降低为(1.33±0.36)mg/L,P<0.01;AUC0→24由(70.72±9.62)mg.L-1.h-1明显降低为(15.82±4.01)mg.L-1.h-1,P<0.01;粪便中排泄药物量由(29.20±5.77)μg明显提高为(198.2±38.07)μg,P<0.01;小丸组在大鼠结肠内容物的药物相对靶向释药指数为30.34。结论地塞米松羧甲基魔芋胶小丸具有结肠定位释药特性。

Studies on in vivorelease of dexamethasone from carboxymethyl konjac glucomannan pellets in rats

Objective To study in vivo release of dexamethasone(Dex) from carboxymethyl konjac glucomannan(CMKGM) pellets and evaluate colon-specific drug delivery characteristics of the pellets.Methods Compared with Dex containing carboxymethyl cellulose suspension,the concentration of Dex in plasma and dejecta after intragastric administrated to rats were measured periodically by HPLC,and used to calculate the relative targeting drug delivery index(DDI).Results Compared with the suspension,the Tmax of the pellets was about 1h,the Tmax of drug in plasma shifted from 4h to 8h,the Cmax decreased significantly from(6.46±0.92) mg/L to(1.33 ±0.36) mg/L(P<0.01),the AUC0→24 decreased significantly from(70.72±9.62) mg·L-1·h-1 to(15.82±4.01) mg·L-1·h-1(P<0.01);the amount of drug excreted in dejecting from 0h to 24h after administration increased significantly from(29.20±5.77) μg to(198.2±38.07) μg(P<0.01).The DDI value of the pellets to deject was 30.34 against the suspension.Conclusion Dex-containing CMKGM pellets may have the location delivery properties.