姜黄素固体分散体在猪体内的比较药动学研究

本研究首次建立了测定猪血浆中姜黄素的高效液相色谱串联质谱法（HPLC-MS/MS）,比较了在内服给药途径下,姜黄素固体分散体和姜黄素预混剂在仔猪体内的药动学特征。选用16头7周龄左右健康二元杂交猪（约克夏×长白）,公母各半,随机分为2组,每组8头,按100 mg·kg^-1（以姜黄素计）分别灌服姜黄素固体分散剂和姜黄素预混剂,不同时间点采集血浆样品,经提取、净化后采用HPLC-MS/MS测定血浆中姜黄素的药物浓度,使用WinNonlin 5.2.1软件非房室模型计算、分析姜黄素在猪体内的药动学参数。结果显示,仔猪灌服姜黄素固体分散体和姜黄素预混剂后的药时曲线下面积（AUC）分别为（104.53±38.67）和（37.82±11.48）h·ng·mL^-1;达峰时间（T_max）分别为（3.25±0.38）和（2.31±0.37）h;峰浓度（C_max）分别为（26.65±9.65）和（9.55±2.75）ng·mL^-1;消除半衰期（t_1/2β）分别为（3.55±2.17）和（6.93±0.86）h;平均驻留时间（MRT）分别为（5.23±0.53）和（4.26±0.47）h,统计分析表明,与预混剂相比,仔猪灌服姜黄素固体分散体后,主要药动学参数差异显著（P<0.01）,T_max明显延迟,C_max显著提高,AUC明显增大,姜黄素固体分散体的相对生物利用度为280.39%。结果表明,姜黄素固体分散体可改善姜黄素在肠道的吸收,提高姜黄素的生物利用度,为今后姜黄素固体分散体的开发和临床应用提供科学依据。

Pharmacokinetics of Curcumin Solid Dispersion in Piglets

A method for the detection of curcumin in pig plasma by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established firstly and the pharmacokinetics of curcumin solid dispersion and curcumin premix in piglets were studied. Sixteen healthy piglets (Yorkshire×Changbai), seven-week aged, half male and half female, were randomly divided into two groups receiving curcumin solid dispersant and curcumin premix orally at the dose of 100 mg·kg^-1, respectively. Then plasma samples were collected at different time points, and the blood concentration of curcumin was determined by HPLC-MS/MS. The WinNonlin 5.2.1 software was used to analyze and calculate the pharmacokinetic parameters. The pharmacokinetic parameters of curcumin solid dispersion and curcumin premix were as follows: the area under the curve (AUC) was (104.53±38.67) and (37.82±11.48) h·ng·mL^-1, time to peak concentration (T_max) was (3.25±0.38) and (2.31±0.37) h, peak concentration (C_max) was (26.65±9.65) and (9.55±2.75) ng·mL^-1, respectively, elimination half-life time (t_1/2β) was (3.55±2.17) and (6.93±0.86) h, mean residence time (MRT) was (5.23±0.53) and (4.26±0.47) h. The statistical analysis showed significant differentce (P<0.01) between curcumin solid dispersion and premix in parameters, the T_max of curcumin solid dispersion was delayed significantly, the C_max was increased obviously and the AUC was improved after the piglets were given curcumin solid dispersion. Compared with curcumin premix, the relative bioavailability of curcumin solid dispersion was 280.39%. The results showed that curcumin solid dispersion could improve the dissolution and absorption of curcumin in the intestinal tract and improve the relative bioavailability of curcumin, which provided a scientific basis for the development and clinical application of curcumin solid dispersions in the future.