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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

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Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors and Affiliations

  1. Department of Pharmaceutics, 302 Hospital of Chinese People’s Liberation Army, Beijing, 100039, China

    Jun-lan Lv  (吕俊兰), Shi-ying Jin  (靳世英), Hai-long Yuan  (袁海龙), Shan-shan Fu  (付珊珊), Jin Han  (韩 晋), Shi-xiao Jin  (靳士晓) & Xiao-he Xiao  (肖小河)

  2. School of Pharmaceutics, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China

    Jun-lan Lv  (吕俊兰), Shi-ying Jin  (靳世英), Shan-shan Fu  (付珊珊) & Shi-xiao Jin  (靳士晓)

  3. Animal Laboratory Center, 302 Hospital of Chinese People’s Liberation Army, Beijing, 100039, China

    Rui-sheng Li  (李瑞生)

Authors
  1. Jun-lan Lv  (吕俊兰)
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  2. Rui-sheng Li  (李瑞生)
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  3. Shi-ying Jin  (靳世英)
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  4. Hai-long Yuan  (袁海龙)
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  5. Shan-shan Fu  (付珊珊)
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  6. Jin Han  (韩 晋)
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  7. Shi-xiao Jin  (靳士晓)
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  8. Xiao-he Xiao  (肖小河)
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Corresponding author

Correspondence to Hai-long Yuan  (袁海龙).

Additional information

Supported by the National Natural Science Foundation of China (No. 81073069)

LU Jun-lan and LI Rui-sheng contributed equally to this work

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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

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  • DOI: https://doi.org/10.1007/s11655-012-1272-8

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