目的: 考察马钱子碱、马钱子总生物碱和优化马钱子总生物碱凝胶剂经皮给药后在小鼠体内的药动学过程。方法: 建立测定小鼠血浆中马钱子碱质量浓度的HPLC法,比较含相同剂量(10.8 mg/kg)马钱子碱各凝胶剂经皮给药后, 马钱子碱的血药浓度, 并对结果进行药动学拟合。结果: 经皮给药后马钱子生物碱类成分的药动学行为均符合二室模型。优化马钱子总生物碱凝胶剂能显著增加马钱子碱的体内吸收, 相对生物利用度显著提高, AUC0→t是马钱子碱凝胶剂的1.74倍, 是马钱子总生物碱凝胶剂的1.89倍, 其他药动学参数无显著差异。结论: 以优化马钱子总生物碱经皮给药, 可有效改善单体马钱子碱和总生物碱的体内药动学行为, 有利于对马钱子碱的减毒增效。

Objective: To evaluate the in vivo pharmacokinetics of hydrogels of brucine, total alkaloids, and optimal total alkaloids from the seed of Strychnos nux-vomica by transdermal administration to mice. Methods: A sensitive and specific HPLC method was established to determine the concentration of brucine in mice plasma, and the pharmacokinetics of alkaloids from the seed of S. nux-vomica was compared at the same dose of brucine (10.8 mg/kg) and their results were fitted by pharmacokinetics. Results: Pharmacokinetic parameters showed that brucine behaved as a two-compartment model in three hydrogels after transdermal administration. The hydrogels of optimal total alkaloids had better absorption in contrast with brucine and the total alkaloids, and its relative bioavailability was remarkably increased. Compared with brucine and the total alkaloids from S. nux-vomica, the AUC0-t of theoptimal total alkaloids from S. nux-vomica was 1.74 and 1.89 times, respectively. Conclusion: The optimal total alkaloids could show greater superiority than the total alkaloids and improve the pure brucine on the in vivo pharmacokinetic properties after transdermal administration, which indicates that a transdermal formulation of the optimal total alkaloids from S. nux-vomica could be a promising candidate aimed at reducing toxicity and enhancing its therapeutic efficacy.

国家科技部“十一五”重大新药创制专项项目(2009ZX09103-342)