炼蜜用量对附子理中丸中9种生物碱类成分药代动力学的影响

甘嘉荷; 王淳; 宋志前; 刘元艳; 宁张弛; 马新玲; 赵思宇; 刘振丽

doi:10.13422/j.cnki.syfjx.2018030090

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炼蜜用量对附子理中丸中9种生物碱类成分药代动力学的影响

药物代谢 | 更新时间：2024-01-04

- 炼蜜用量对附子理中丸中9种生物碱类成分药代动力学的影响
- Effect of Refined Honey Amount on Pharmacokinetics of 9 Different Alkaloids in Fuzi Lizhongwan
- 中国实验方剂学杂志 2018年24卷第3期页码：90-96
- 作者机构：
- 作者简介：
- 基金信息：
  
  中央级科研院所自主选题项目（YZ-1542）
- DOI：10.13422/j.cnki.syfjx.2018030090
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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甘嘉荷, 王淳, 宋志前, 等. 炼蜜用量对附子理中丸中9种生物碱类成分药代动力学的影响[J]. 中国实验方剂学杂志, 2018,24(3):90-96.

GAN Jia-he, WANG Chun, SONG Zhi-qian, et al. Effect of Refined Honey Amount on Pharmacokinetics of 9 Different Alkaloids in Fuzi Lizhongwan[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(3): 90-96.
甘嘉荷, 王淳, 宋志前, 等. 炼蜜用量对附子理中丸中9种生物碱类成分药代动力学的影响[J]. 中国实验方剂学杂志, 2018,24(3):90-96. DOI： 10.13422/j.cnki.syfjx.2018030090.

GAN Jia-he, WANG Chun, SONG Zhi-qian, et al. Effect of Refined Honey Amount on Pharmacokinetics of 9 Different Alkaloids in Fuzi Lizhongwan[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(3): 90-96. DOI： 10.13422/j.cnki.syfjx.2018030090.

摘要

目的：建立大鼠口服附子理中丸2种剂型后不同时间点血浆中9种生物碱类成分含量的测定方法，考察辅料炼蜜对附子中主要生物碱类成分药代动力学行为的影响。方法：SD大鼠分别给予2种含炼蜜量不同的附子理中丸大蜜丸（19.44 g·kg-1）和水蜜丸（19.22 g·kg-1），于给药后不同时间点取血，采用RRLC-TQ-MS测定血浆中9种生物碱类成分的血药浓度，绘制血药浓度-时间曲线，计算药物动力学参数。结果：在大鼠血浆中检测到9种生物碱中的8种。双酯型生物碱乌头碱、新乌头碱、次乌头碱的药-时曲线下面积（AUC），药峰浓度（Cmax），达峰时间（Tmax）和半衰期（t1/2）均为大蜜丸>水蜜丸，而清除率（CL）为大蜜丸Tmax和t1/2均为大蜜丸Cmax和CL为大蜜丸>水蜜丸，苯甲酰乌头原碱未被检测到；醇胺型生物碱乌头原碱、新乌头原碱和次乌头原碱的AUC，Tmax和t1/2均为大蜜丸Cmax和CL为大蜜丸>水蜜丸。结论：炼蜜能够影响附子理中丸中制附子主要生物碱成分的药动学特征，炼蜜量大的大蜜丸与炼蜜量小的水蜜丸比较，作为制附子的特征性标志物双酯型生物碱在体内达到药峰时间延长，消除速度减慢，提示炼蜜在复方中能够起到延缓吸收的作用。

Abstract

Objective:To establish a method for the determination of nine alkaloids in plasma at different time points after oral administration of two dosage forms of Fuzi Lizhongwan

in order to determine refined honey whether have any impact on the pharmacokinetic behavior of the main alkaloids. Method:SD rats were given two different kinds of Fuzi Lizhongwan(big honeyed pill of 19.44 g·kg-1 and water-honeyed pill of 19.22 g·kg-1) with different amount of honey.Blood concentrations were measured at different time points after administration

and the concentrations of 9 alkaloids in the plasma were determined by RRLC-TQ-MS.The plasma concentration-time curves were drawn and the pharmacokinetic parameters were calculated. Result:Eight of nine alkaloids were detected in rat plasma.For diester alkaloids

the AUC

Cmax

Tmax and t1/2 of aconitine

mesaconitine and hypaconitine were big honeyed pill>water-honeyed pill

and clearance rate(CL) was the big honeyed pillTmax and t1/2 of benzoylmesaconine and benzoylhypaconine were big honeyed pillCmax and CL were big honeyed pill >water-honeyed pill.Benzoylaconine was not detected.For alcohol amine alkaloids

the AUC

Tmax and t1/2 of aconine

mesaconine and hypaconine were big honeyed pill< water-honeyed pill

and Cmax and CL were big honeyed pill>water-honeyed pill. Conclusion:The refined honey can affect the pharmacokinetic characteristics of the main alkaloid components in Fuzi Lizhongwan.Compared with the water-honeyed pill

times to peak of diester alkaloids in big honeyed pill are extended and the elimination rates are slowed down

which suggesting that refined honey in the formula can play a role in delaying absorption.

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