title: Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal ointment Liu-He-Dan in anaesthetized rats.
abstract: BACKGROUND
  Chinese herbal preparation of Liu-He-Dan ointment has been adapted for acute pancreatitis in external application for many years in West China.
  
  
  OBJECTIVE
  To investigate the effect of acute pancreatitis on the pharmacokinetics of Liu-He-Dan ointment in rats while it was used externally on belly.
  
  
  METHODS
  Twelve male Sprague-Dawley rats were randomly divided into acute pancreatitis model group (n=6) and normal group as a control (n=6). Chinese herbal Liu-He-Dan ointment was used externally on belly. Emodin, rhein, aloe emodin, physcion and chrysophanol in plasma and pancreas (at 48 h) were detected and quantified by liquid chromatography-tandem mass spectrometry. Amylase in plasma were determined with iodide process.
  
  
  RESULTS
  Among the five components, only emodin, aloe emodin and physcion from Liu-He-Dan were detected in plasma and pancreas. The absorption of each component was tended to decrease in acute pancreatitis group after topically management with Liu-He-Dan ointment on rats' abdomen. The T(max), C(max) and area under curve (AUC) of each component were distinctly lower in AP group than those in normal group (p<0.05). However, the T(1/2α) and mean retention time (MRT) of emodin lasted longer in acute pancreatitis group than those in normal group (p<0.05). There was no statistical difference in the MRT of aloe emodin and physcion between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in acute pancreatitis model group than in normal group (0.91 ± 0.68, 0.41 ± 0.36, respectively). Physcion could be detected in pancreas of most acute pancreatitis models, but not in normal rats. Aloe emodin was found in all pancreas from acute pancreatitis models while only one in normal group. The level of amylase in Liu-He-Dan group was obviously lower than that in the AP model group (p=0.0055).
  
  
  CONCLUSIONS
  We concluded that acute pancreatitis may significantly affect the pharmacokinetics of Liu-He-Dan while external applied on belly, which indicated the dosage modification in AP. However, acute pancreatitis seems to promote the distribution of the detected components into pancreas. The ointment could help relieve the disease of pancreatitis.
authors.affiliation: Department of Integrative Medicine, Sichuan University, Sichuan Province, Chengdu 610041, China.
authors.forename: Xian-Lin
authors.initials: XL
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Xiang
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Wan
authors.forename: Qin
authors.initials: Q
authors.lastname: Yu
authors.forename: Wei-wei
authors.initials: WW
authors.lastname: Chen
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Chen
authors.forename: Wen-Fu
authors.initials: WF
authors.lastname: Tang
mesh_terms: D000279:Administration, Cutaneous; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000493:pharmacokinetics; D001120:Arginine; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004642:Emodin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D009824:Ointments / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000880:Anthraquinones; D004365:Drugs, Chinese Herbal; C581590:Liu-He-Dan; D009824:Ointments; D001120:Arginine; C518327:aloe emodin; D000681:Amylases; C008905:physcione; D004642:Emodin; C020491:rhein