Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102)

doi:10.1007/s13318-018-0515-5

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	Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102)
	Qing, Lin-Sen 3; Chen, Ting-Bo 2; Sun, Wen-Xia 1; Chen, Li 2; Luo, Pei 2; Zhang, Zhi-Feng 2; Ding, Li-Sheng 3
刊名	EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
	2019
卷号	44 期号:2 页码:251-259
ISSN号	0378-7966
DOI	10.1007/s13318-018-0515-5
产权排序	1
文献子类	Article
英文摘要	Background and ObjectivesAstragaloside IV (AGS IV) is the most important bioactive constituent of Radix Astragali. However, its disappointing clinical application is mainly caused by its very low solubility in biologic fluids, resulting in poor bioavailability after oral administration. We recently obtained a novel water-soluble derivative of AGS IV (astragalosidic acid, LS-102) that displayed significant cardioprotective potential against hypoxia-induced injury. The objective of this study was to investigate the intestinal absorption, main pharmacokinetic parameters and acute toxicity of LS-102 in rodents compared with AGS IV.MethodsAn oral dose of LS-102 and AGS IV (20mg/kg) was administered to Sprague-Dawley (SD) rats, and blood samples were collected at predetermined time points. The plasma concentrations were detected by a validated UHPLC-MS/MS method, and pharmacokinetic parameters were calculated using a compartmental model. In the intestinal permeability study, the transport of LS-102 across Caco-2 cell monolayers was investigated at six concentrations from 6.25 to 250 mu M. Moreover, the acute toxicity of LS-102 (40-5000mg/kg) via a single oral administration was investigated in BALB/c mice.ResultsLS-102 was rapidly absorbed, attaining a maximum concentration of 248.722.0ng/ml at 1.0 +/- 0.5 h after oral administration. The relative bioavailability of LS-102 was twice that of AGS IV. LS-102 had a P-app (mean) of 15.72-25.50x10(-6) cm/s, which was almost 500-fold higher than that of AGS IV, showing that LS-102 had better transepithelial permeability and could be better absorbed in the intestinal tract. The acute toxicity study showed no abnormal changes or mortality in mice treated with LS-102 even at the single high dose of 5000mg/kg body weight.Conclusions p id=Par4 Oral LS-102 produced a pharmacokinetic profile different from AGS IV with higher bioavailability, while the toxic tolerance was similar to previous estimates. Thus, we speculated that LS-102 might provide better clinical efficacy and be a potential candidate for the new drug development of Radix Astragali.
学科主题	Pharmacology & Toxicology
URL标识	查看原文
WOS关键词	RAT PLASMA ; TRANSPORT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	SPRINGER FRANCE
WOS记录号	WOS:000461290500010
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/31057]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Chengdu Univ, Antibiot Res & Reevaluat Key Lab Sichuan Prov, Sichuan Ind Inst Antibiot, Chengdu, Sichuan, Peoples R China 2.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Ave Wai Long, Taipa, Macau, Peoples R China; 3.Chinese Acad Sci, Chengdu Inst Biol, Chengdu, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Qing, Lin-Sen,Chen, Ting-Bo,Sun, Wen-Xia,et al. Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102)[J]. EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS,2019,44(2):251-259.
APA	Qing, Lin-Sen.,Chen, Ting-Bo.,Sun, Wen-Xia.,Chen, Li.,Luo, Pei.,...&Ding, Li-Sheng.(2019).Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102).EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS,44(2),251-259.
MLA	Qing, Lin-Sen,et al."Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102)".EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 44.2(2019):251-259.