雷公藤内酯醇与不同种属血浆蛋白结合率的研究

Plasma protein binding characteristics of triptolide in several species

目的考察雷公藤内酯醇在不同种属的血浆蛋白结合率。方法超滤法分离结合型药物和游离型药物,LC-MS/MS法测定药物的浓度。结果雷公藤内酯醇在不同浓度下与大鼠血浆的蛋白结合率分别是(25.4±1.8)、(12.7±8.5)和(11.5.±3.2)ng/ml,与比格犬血浆的蛋白结合率分别是(16.1±2.2)、(28.6±0.3)和(25.0±1.2)ng/ml;与人血浆的蛋白结合率分别是(21.5±2.1)、(18.9±5.7)和(21.3±2.6)ng/ml。结论雷公藤内酯醇在实验浓度范围内与大鼠、比格犬和人血浆中蛋白结合率均较低,相同浓度雷公藤内酯醇与不同种属血浆蛋白结合率,以犬血浆最高[(28.6±0.3)ng/ml],与大鼠[(25.4±1.8)ng/ml]、人血浆[(18.9±5.7)ng/ml]相比均具有统计学差异(P<0.05),大鼠与人血浆之间无统计学差异。各种属血浆蛋白结合率与药物浓度无明显依赖关系。

Objective To study the regularity of the plasma protein binding rate of triptolide （TP） in several species. Methods Ultrafiltration was employed to determine the plasma protein binding rate of triptolide in several species. Results The plasma protein binding rate of TP was 25.4 ± 1.8, 12.7 ± 8.5 and 11.5 ± 3.2 ng/ml in rat, 16.1 ± 2.2, 28.6 ± 0.3 and 25.0 ± 1.2 ng/ml in Beagles and 21.5 ±2.1, 18.9 ±5.7 and 21.3 ±2.6 ng/ml in humans, respectively. Conclusion TP has a lower plasma protein binding rate in several species and the highest binding rate is showed in the dog plasma at the same concentration of 40 ng/ml. There is statistic difference between dog, rat and human plasma （ P 〈 0.05 ）. The protein binding rates are not proportionally dependent on plasma concentrations of TP.