五酯软胶囊对西罗莫司在大鼠体内药动学的影响

Effects of Wuzhi Soft Capsule on the Pharmacokinetics of Sirolimus in Rats

目的:考察五酯软胶囊对西罗莫司在大鼠体内药动学的影响。方法:取Wistar大鼠随机分为5组,每组6只,分别按极低、低、中、高剂量(67、134、268、536 mg/kg)ig五酯软胶囊内容物或空白溶剂,0.5 h后再ig西罗莫司0.4 mg/kg。分别于西罗莫司给药前(0 h)和给药后0.5、0.75、1、1.5、2、2.5、3、4、6、8、12、24、36 h毛细管眼眶取全血100μl于乙二胺四乙酸抗凝试管中,采用液相色谱-质谱联用法测定全血中西罗莫司的浓度,采用DAS 2.0药动学软件以非隔室模型计算药动学参数。结果:极低、低、中、高剂量组和溶剂对照组大鼠体内西罗莫司的药动学参数cmax为(6.79±1.15)、(17.40±3.13)、(21.24±3.14)、(22.06±4.82)、(2.80±0.72)ng/ml;t1/2为(11.01±0.82)、(12.20±2.02)、(12.28±2.38)、(12.36±0.73)、(10.59±0.69)h;AUC0-∞为(85.79±15.26)、(162.18±41.75)、(273.12±73.69)、(268.79±28.46)、(36.72±3.01)ng·h/ml。与溶剂对照组比较,极低、低、中、高剂量组大鼠体内西罗莫司的cmax和AUC0-∞均升高,但t1/2变化不明显。结论:五酯软胶囊可明显促进西罗莫司在大鼠体内的吸收。

OBJECTIVE：To investigate the effect of Wuzhi soft capsule on the pharmacokinetics of sirolimus in rats. METHODS：Wistar rats were randomly divided into 5 groups,with 6 rats in each group. They were given very low-dose,low-dose,medium-dose and high-dose of Wuzhi soft capsule（67,134,268 and 536 mg/kg）ig or blank solvent,respectively;and then given sirolimus 0.4 mg/kg. The blood 100 μl was sampled by capillary eyes before giving sirolimus（0 h）and 0.5,0.75,1,1.5,2,2.5,3,4,6,8,12,24 and 36 h after giving sirolimus and put into edetic acid anticoagulation tube. Blood concentration of sirolimus was assayed by LC-MS/MS. The pharmacokinetic parameter was calculated by DAS 2.0 software using non-compartment model.RESULTS：The pharmacokinetic parameters of sirolimus in very low-dose,low-dose,medium-dose and high-dose groups and blank solvent group were cmaxof（6.79±1.15）,（17.40±3.13）,（21.24±3.14）,（22.06±4.82）,（2.80±0.72）ng/ml;t1/2of（11.01±0.82）,（12.20±2.02）,（12.28±2.38）,（12.36±0.73）,（10.59±0.69）h;AUC0-∞of（85.79±15.26）,（162.18±41.75）,（273.12±73.69）,（268.79±28.46）,（36.72±3.01）ng·h/ml,respectively. Compared with blank solvent group,cmaxand AUC0-∞of sirolimus were all increased in very low-dose,low-dose,medium-dose and high-dose groups,but t1/2changed slightly. CONCLUSIONS：Wuzhi soft capsule can substantially enhance the absorption of sirolimus in rats.