title: Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.
abstract: BACKGROUND
  Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis.
  
  
  OBJECTIVE
  To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY.
  
  
  METHODS
  Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats.
  
  
  RESULTS
  A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (P<0.05). Tissue distribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (P<0.05). Meanwhile, the result also reveals that the hepatic fibrosis could delay the peak time of lignans in liver.
  
  
  CONCLUSIONS
  The results proved that the established UHPLC-MS/MS method could be applied to the comparative study on pharmacokinetics and tissue distribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine.
authors: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
authors: Tao
authors: T
authors: Yang
authors: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Shan
authors: S
authors: Liu
authors: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors: Tian-Hui
authors: TH
authors: Zheng
authors: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai 201203, China; E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, 1200 Cailun Road, Shanghai 201203, China.
authors: Yan-Yan
authors: YY
authors: Tao
authors: Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai 201203, China; E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, 1200 Cailun Road, Shanghai 201203, China. Electronic address: chenghailiu@hotmail.com.
authors: Cheng-Hai
authors: CH
authors: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D034242:Cyclooctanes / Q000493:pharmacokinetics / Q000494:pharmacology; D004149:Dioxoles / Q000493:pharmacokinetics / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D017705:Lignans / Q000493:pharmacokinetics* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D011083:Polycyclic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D034242:Cyclooctanes; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011083:Polycyclic Compounds; C532829:fuzheng huayu; C520474:schisandrol A; C015499:schizandrin B; C033585:schizandrol B; C034734:schizandrin A; C034557:schizandrer A; C031409:schizandrin C
keywords: Fuzheng Huayu recipe; Hepatic fibrosis; Lignan; Pharmacokinetics; Tissue distribution; UHPLC-MS/MS