title: Effect of Huang-Lian-Jie-Du-Decoction on pharmacokinetics of verapamil in rats.
abstract: OBJECTIVE
  The aim was to investigate the effect of Huang-Lian-Jie-Du-Decoction (HLJDD) on the pharmacokinetic behaviour of verapamil in rats.
  
  
  METHODS
  Rats orally received 3.33 g/kg of HLJDD extract for 14 days, and pharmacokinetics of verapamil was investigated after oral and intravenous verapamil. Norverapamil formation for assessing cytochrome P450 3A activity in hepatic and intestinal microsomes of the HLJDD-treated rats was investigated. The inhibitory effect of berberine on the formation of norverapamil in intestinal and hepatic microsomes was also evaluated.
  
  
  RESULTS
  HLJDD treatment increased the plasma concentration of verapamil and decreased the plasma concentration of norverapamil, resulting in a 24% increase in the AUC(0-480) of verapamil and a 25% reduction in the AUC(0-480) of norverapamil after oral administration. However, HLJDD did not alter the pharmacokinetic behaviour of verapamil after intravenous administration. Norverapamil formation showed biphasic kinetics in both intestinal and hepatic microsomes. HLJDD treatment significantly decreased the intrinsic clearance of verapamil in intestinal microsomes, but had no effect on the hepatic metabolism of verapamil. Berberine also inhibited norverapamil formation in both intestinal and hepatic microsomes; the extent of inhibition was larger in intestinal microsomes.
  
  
  CONCLUSIONS
  HLJDD displayed a route-dependent effect on the pharmacokinetics of verapamil in rats. HLJDD treatment increased the bioavailability of verapamil partly via inhibiting first-pass verapamil metabolism in the intestine.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xie
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Jing
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
authors.forename: Chang-Hui
authors.initials: CH
authors.lastname: Liu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001599:Berberine / Q000494:pharmacology*; D001682:Biological Availability; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D008658:Inactivation, Metabolic; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D019684:Magnoliopsida; D008297:Male; D008861:Microsomes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D004365:Drugs, Chinese Herbal; C061676:oren gedoku to; D001599:Berberine; C016904:norverapamil; D014700:Verapamil; D051544:Cytochrome P-450 CYP3A