Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice

ZHANG Mi; LI Lu-jin; LV Ying-hua; ZHENG Qing-shan

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Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice

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- Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 16, Issue 4, Pages: 95-99(2010)
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- Published：2010
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ZHANG Mi, LI Lu-jin, LV Ying-hua, et al. Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice[J]. Chinese journal of experimental traditional medical formulae, 2010, 16(4): 95-99.
DOI：

ZHANG Mi, LI Lu-jin, LV Ying-hua, et al. Quantitative evaluation of the anticonvulsant effects and toxicity of pinellia total alkaloid and uncaria total alkaloid in combination in mice[J]. Chinese journal of experimental traditional medical formulae, 2010, 16(4): 95-99. DOI：

摘要

目的 :利用已发表的半夏生物总碱(pinellia total alkaloid

PTA)与钩藤生物总碱(uncaria total alkaloid

UTA)联合抗惊厥和毒性作用数据

全面定量评价其相互作用和组方合理性。方法: 采用等效图法(isobologram)和计算机模拟技术

定量评价不同强度(0%~99%)有效剂量(ED)和致死剂量(LD)的相互作用

并综合计算其获益指数(BI)和治疗指数(TI)。结果: 3个配比(PTA ∶UTA=1 ∶4

1 ∶1

4 ∶1)有协同作用趋势。由于最高剂量的有效率均低于70%

给参数计算和研究结论带来不确定性。PTA和UTA按4 ∶1联用的毒性呈现拮抗作用

其它2个配比毒性拮抗作用不明确。基于ED和LD参数的综合分析

3个配比的BI均大于1

其中4 ∶1配比的减毒增效作用明确

TI增大。结论: PTA和UTA按4 ∶1给药后安全性和有效性提高

呈现配伍优势。从方法学角度

本研究可对同类实验的设计和分析提供参考。

Abstract

Objective: To make a comprehensive and quantitative evaluation of the interactions at different ratios between pinellia total alkaloid (PTA) and uncaria total alkaloid (UTA) based on the published data of anticonvulsant and toxicity in combinations. Method: The isobologram and a computer simulation have been used to analyze the interactions of the different levels ED and LD in the combinations. Result: Combinations in the three ratios (PTA ∶UTA=1 ∶4

1 ∶1

4 ∶1) show a synergistic trend. However

it is difficult to obtain accurate parameters because of the responses (ED

%) at the maximum dose are less than 70%. Combinatin in the ratio of PTA ∶UTA=4 ∶1 shows an antagonism in toxicity

and at other two ratios (1 ∶4

1 ∶1) the combinations do not provide robust results. In the comprehensive efficacy and toxicity of quantitative parameters

the values of benefit index (BI) in all three ratios are more than 1. The ratio of PTA ∶UTA=4 ∶1 could reduce toxicity and increase efficacy. Conclusions : The combination at the ratio of PTA ∶UTA=4 ∶1 shows a significant advantage at the safety and efficacy. This study also provides the performance of methods for design and analysis.

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Related Author

ZHANG Mi

LI Lu-jin

LV Ying-hua

ZHENG Qing-shan

Juan XUE

Qing WEI

Shan-shan LIANG

Long-jiang LIU

Related Institution

Department of Pharmacometrics,Center for Drug Clinical Research,Shanghai University of Chinese Medicine

Guizhou University of Traditional Chinese Medicine

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