Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment

Jun-lan Lv; Rui-sheng Li; Shi-ying Jin; Hai-long Yuan; Shan-shan Fu; Jin Han; Shi-xiao Jin; Xiao-he Xiao

doi:10.1007/s11655-012-1272-8

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Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment

Updated：2021-08-27

- Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment
- Chinese Journal of Integrative Medicine Vol. 18, Issue 11, Pages: 831-836(2012)
- Affiliations：
  
  1. Department of Pharmaceutics, Hospital of Chinese People’s Liberation Army,Beijing,China,302
  2. School of Pharmaceutics, Chengdu University of Traditional Chinese Medicine,Chengdu,China
  3. Animal Laboratory Center, Hospital of Chinese People’s Liberation Army,Beijing,China,302
- Author bio：
- Funds：
  
  Supported by the National Natural Science Foundation of China (No. 81073069);LU Jun-lan and LI Rui-sheng contributed equally to this work
- DOI：10.1007/s11655-012-1272-8
  CLC：
- Published：2012，
  
  Published Online：20 October 2012，
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Lv, Jl., Li, Rs., Jin, Sy. et al. Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment., Chin. J. Integr. Med. 18, 831–836 (2012). https://doi.org/10.1007/s11655-012-1272-8

Jun-lan Lv, Rui-sheng Li, Shi-ying Jin, et al. Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment. [J]. Chinese Journal of Integrative Medicine 18(11):831-836(2012)
Lv, Jl., Li, Rs., Jin, Sy. et al. Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment., Chin. J. Integr. Med. 18, 831–836 (2012). https://doi.org/10.1007/s11655-012-1272-8 DOI：

Jun-lan Lv, Rui-sheng Li, Shi-ying Jin, et al. Changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate-induced experimental hepatic injury after Yinchenhao Decoction (茵陈蒿汤) treatment. [J]. Chinese Journal of Integrative Medicine 18(11):831-836(2012) DOI： 10.1007/s11655-012-1272-8.

摘要

To study the changes of pharmacokinetics of 6

7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate (ANIT)-induced experimental hepatic injury after oral administration of Yinchenhao Decoction (茵陈蒿汤

YCHD) using an ultra pressure liquid chromatography (UPLC) method. Rats were divided into a normal group and a model group

after modeled by 4% ANIT (75 mg/kg) for 48 h

they were orally administrated with YCHD extract at the dose of 0.324 g/kg

and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase (ALT)

aspartate aminotransferase (AST)] and bilirubins [total bilirubin (TBIL)

direct bilirubin (DBIL)]

the concentration of 6

7-dimethoxycoumarin in plasma were measured by UPLC

and the pharmaceutical parameters were calculated with DAS2.1.1 software. The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained. Their time to maximum plasma concentration (tmax) were both 0.25 h

the maximum concentration (Cmax) were 4.533 μg/mL and 6.885 μg/mL

and their area under concentration-time curve (AUC)0→24h were 16.272 and 32.981

respectively. There was a 51.88% and 100.46% increase in Cmax and AUC0-t (P<0.05)

but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution (P<0.05)

respectively. Hepatic injury could significantly influence the pharmacokinetics of 6

7-dimethoxycoumarin after oral administration of YCHD

the absorption and distribution process was accelerated in liver injured rats

but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6

7-dimethoxycoumarin in the body.

Abstract

To study the changes of pharmacokinetics of 6

7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate (ANIT)-induced experimental hepatic injury after oral administration of Yinchenhao Decoction (茵陈蒿汤

YCHD) using an ultra pressure liquid chromatography (UPLC) method. Rats were divided into a normal group and a model group

after modeled by 4% ANIT (75 mg/kg) for 48 h

they were orally administrated with YCHD extract at the dose of 0.324 g/kg

and then blood was collected from their orbital sinus after different intervals. Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase (ALT)

aspartate aminotransferase (AST)] and bilirubins [total bilirubin (TBIL)

direct bilirubin (DBIL)]

the concentration of 6

7-dimethoxycoumarin in plasma were measured by UPLC

the maximum concentration (Cmax) were 4.533 μg/mL and 6.885 μg/mL

and their area under concentration-time curve (AUC)0→24h were 16.272 and 32.981

respectively. There was a 51.88% and 100.46% increase in Cmax and AUC0-t (P<0.05)

but there showed a 45.52% and 92.93% reduction in clearance of drug and volum of distribution (P<0.05)

respectively. Hepatic injury could significantly influence the pharmacokinetics of 6

7-dimethoxycoumarin after oral administration of YCHD

the absorption and distribution process was accelerated in liver injured rats

but the metabolism and elimination process was slowed. And this may lead to a significant accumulation of 6

7-dimethoxycoumarin in the body.

关键词

hepatic injury67-dimethoxycoumarinYinchenhao Decoctionpharmacokineticsultra pressure liquid chromatography

Keywords

hepatic injury67-dimethoxycoumarinYinchenhao Decoctionpharmacokineticsultra pressure liquid chromatography

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