姜黄素在大鼠体内药代动力学和生物利用度研究

Pharmacokinetics and absolute bioavailability of curcumin in rats

目的研究姜黄素不同给药途径在大鼠体内的药代动力学和绝对生物利用度。方法建立大鼠血浆中姜黄素的HPLC检测方法。考察大鼠分别经灌胃ig(200 mg·kg-1)、ip腹腔注射(20 mg·kg-1)、舌下静脉iv(10 mg·kg-1)给予姜黄素后血药浓度变化。用DAS2.0软件计算药动学参数,根据腹腔注射、灌胃和静脉给药药-时曲线下面积AUC(0-∞)和给药剂量,计算腹腔注射和口服姜黄素的绝对生物利用度。结果姜黄素浓度在0.05～6.00 mg·L-1范围内线性关系良好(r=0.9998);定量下限为0.05 mg·L-1;低(0.10 mg·L-1)、中(1.00 mg·L-1)、高(4.00 mg·L-1)3个浓度的回收率分别为(99.29±5.40)%、(104.21±4.72)%和(99.83±1.97)%;日内RSD分别为4.49%、3.90%和1.72%,日间RSD分别为4.61%、4.27%和2.00%。大鼠经灌胃、腹腔注射和静脉注射姜黄素后,姜黄素在大鼠体内的代谢过程均符合二室模型,消除半衰期分别为(159.28±18.12)、(90.79±11.55)和(11.96±2.64)min;AUC(0-∞)分别为(86.36±12.90)、(73.39±8.72)、(104.62±11.89)mg.min.L-1。按剂量折算,姜黄素经腹腔注射给药的绝对生物利用度为35.07%,灌胃给药的绝对生物利用度为4.13%。结论姜黄素经不同途径给药在大鼠体内的药代动力学过程相似,腹腔注射给药的绝对生物利用度较高,口服生物利用度低。

Aim To study the pharmacokinetics and absolute bioavailability of curcumin in rats with different administration.Methods A HPLC method was developed for the determination of curcumin in rat plasma.Oral,intraperitoneal and ranine vein doses of 200,20 mg·kg-1 and 10 mg·kg-1 were respectively administered,and the concentrations of curcumin were determined with HPLC.The pharmacokinetic parameters were calculated with the program DAS 2.0.The absolute bioavailability of curcumin was calculated according to AUC（0-∞） and the doses of curcumin following oral,intravenous and intraperitoneal administration.Results Excellent linear relationship was obtained in the range of 0.05~6.00 mg·L-1（r=0.9998）.The lower limit determination of curcumin was 0.05 mg·L-1.The relative recoveries were（99.29±5.40）%,（104.21±4.72）% and（99.83±1.97）%respectively at three concentrations（0.10 mg·L-1,1.00 mg·L-1,4.00 mg·L-1）.The intra-day RSD were 4.49%,3.90%and 1.72%.The inter-day RSD were 4.61%,4.27% and 2.00% respectively.The metabolic processes of curcumin in rats all fit in with the two-compartment model following oral,intravenous and intraperitoneal administration.Elimination half life were（159.28±18.12）,（90.79±11.55）,（11.96±2.64） min respectively and AUC（0-∞） were（86.36±12.90） mg·min·L-1,（73.39±8.72） mg·min·L-1,（104.62±11.89） mg·min·L-1 respectively.The absolute bioavailability of intraperitoneal administration was 35.07% and the absolute bioavailability of intragastric administration was 4.13%.Conclusion With different administration,the pharmacokinetics process of curcumin is similar in rats.The absolute bioavailability of intraperitoneal administration is relatively high,while the absolute bioavailability of intragastric administration is low.