Xu Yanyan, Li Yamei, Zhang Pengjie, Yang Bin, Wu Huanyu, Guo Xuejun, Li Yubo, Zhang Yanjun
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jul 15;1058:24-31. doi: 10.1016/j.jchromb.2017.05.016. Epub 2017 May 15.
Aconiti Lateralis Radix Praeparata- Fritillariae Thunbergii bulbus, namely Fuzi- Beimu in Chinese, is a classic herb pair whose combined administration was prohibited according to the rule of "Eighteen antagonisms". However, incompatibility of Fuzi and Beimu has become controversial because of the application supported by many recorded ancient prescriptions and increasing modern researches and clinical practice. The present study aimed to investigate the pharmacokinetic differences of multiple alkaloids from Fuzi- Beimu and the single herb aqueous extracts following oral delivery in rats. Twelve alkaloids including aconitine, mesaconitine, hypaconitine, benzoylaconitine, benzoylmesaconitine, benzoylhypacoitine, neoline, fuziline, talatisamine, chasmanine, peimine and peimisine in rat plasma were simultaneously quantitated by using sensitive ultra-high performance liquid chromatography- tandem mass spectrometry (UHPLC-MS/MS), with the method developed and fully validated. Plasma concentrations of the twelve alkaloids after administration were determined and pharmacokinetic parameters were compared. Significant differences were observed for all alkaloids except aconitine, mesaconitine and benzoylaconitine for Fuzi- Beimu group in comparison with the single herb group. AUC and T of hypaconitine were increased significantly. AUC and C were increased and T decreased significantly for benzoylmesaconitine and benzoylhypacoitine. Fuziline showed significantly increased AUC, C and T. T of neoline was notably increased. T and T were significantly elevated for talatisamine while C decreased. T of chasmanine was significantly increased and C decreased. Extremely significant increase of T was found for peimisine, and significant increase of T for peimine. Results revealed that combined use of Fuzi and Beimu significantly influenced the system exposure and pharmacokinetic behaviors of multiple alkaloids from both herbs, indicating herb- herb interaction between Fuzi and Beimu.
附子-浙贝母，即中药中的附子-贝母，是一对经典药对，根据“十八反”原则，其配伍使用被禁止。然而，由于众多古代方剂记载的支持以及现代研究和临床实践的增多，附子与贝母的配伍禁忌已颇具争议。本研究旨在探讨附子-贝母及单味药水提取物经大鼠口服给药后多种生物碱的药代动力学差异。采用灵敏的超高效液相色谱-串联质谱法（UHPLC-MS/MS）同时定量测定大鼠血浆中的12种生物碱，包括乌头碱、中乌头碱、次乌头碱、苯甲酰乌头碱、苯甲酰中乌头碱、苯甲酰次乌头碱、新乌头碱、附子碱、塔拉胺、查斯曼宁、浙贝母碱和浙贝宁，所建立的方法经过全面验证。测定给药后12种生物碱的血浆浓度并比较药代动力学参数。与单味药组相比，附子-贝母组除乌头碱、中乌头碱和苯甲酰乌头碱外，所有生物碱均观察到显著差异。次乌头碱的AUC和T显著增加。苯甲酰中乌头碱和苯甲酰次乌头碱的AUC和C增加，T显著降低。附子碱的AUC、C和T显著增加。新乌头碱的T显著增加。塔拉胺的T和T显著升高，而C降低。查斯曼宁的T显著增加，C降低。浙贝宁的T极度显著增加，浙贝母碱的T显著增加。结果表明，附子与贝母配伍使用显著影响了两味药中多种生物碱的全身暴露和药代动力学行为。提示附子与贝母之间存在药-药相互作用。
