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目的:研究麻黄-甘草(MH-GC)药对不同配比水煎液灌胃给予大鼠后,血浆中麻黄类生物碱含量的变化。方法:大鼠按体重随机等分成4组,分别为MH,MH-GC(12∶3),MH-GC(12∶6)和MH-GC(12∶12),于给药后不同时间点采血,给药量分别为7.42,9.28,11.13,14.84 g·kg-1。利用液液萃取法处理血浆样品,以盐酸金刚烷胺为内标,采用UPLC-MS/MS测定血浆样品中盐酸去甲基麻黄碱(NME),盐酸去甲基伪麻黄碱(NMP),盐酸麻黄碱(E),盐酸伪麻黄碱(PE)和盐酸甲基麻黄碱(ME)的血药浓度,利用DAS 3.0软件计算药动学参数。结果:与MH组相比,MH-GC(12∶3)组中NME和NMP的MRT0-t得到显著缩短,PE的t1/2z和Vz/F也显著降低;MH-GC(12∶6)组中NME,E和PE的AUC0-t均得到显著提高,PE的CLz/F和Vz/F显著降低;MH-GC(12∶12)组中E和PE的MRT0-t则显著延长,ME的CLz/F显著提高。结论:麻黄与不同比例的甘草配伍后,5种麻黄类生物碱的部分药动学参数具有显著性差异。随着甘草用量的不同,所表现出的减毒或增效侧重点则不同,从药动学角度证明了古方用药针对不同病症药物用量不同的科学性与合理性。
OBJECTIVE: To study the changes of the content of ephedrine alkaloid in plasma after ephedra-licorice (MH-GC) medicine was given to rats with different proportion of decoction. Methods: The rats were randomly divided into 4 groups according to body weight: MH, GC (12:3), MH-GC (12:6) and MH-GC Blood samples were administered at doses of 7.42, 9.28, 11.13 and 14.84 g · kg -1, respectively. Plasma samples were processed by liquid-liquid extraction. Amantadine hydrochloride was used as an internal standard, and plasma samples were collected for determination of NME, NMP, (E), pseudoephedrine hydrochloride (PE) and methyl ephedrine hydrochloride (ME), and the pharmacokinetic parameters were calculated by DAS 3.0 software. Results: MRT0-t of NME and NMP in MH-GC (12:3) group was significantly shortened, while t1 / 2z and Vz / F in PE were also significantly decreased compared with MH group. MH- The AUC0-t of NME, E and PE were significantly increased in group and the CLz / F and Vz / F of PE were significantly decreased. The MRT0-t of E and PE in MH-GC (12:12) The CLz / F significantly increased. Conclusion: Some pharmacokinetic parameters of five kinds of ephedra alkaloids have significant difference after compatibility of ephedra with different proportion of licorice. With the different dosage of licorice, the emphasis on attenuating or increasing efficiency is different, which proves the scientific and rationality that the dosage of ancient prescription medication is different for different diseases from the pharmacokinetic point of view.