title: Da-Chaihu-Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this.
abstract: OBJECTIVE
  To investigate the influence of co-administrated Da-Chaihu-Tang (DCT; a traditional Chinese formulation) on the pharmacokinetics of nifedipine, as well as the safe optimal dosing interval to avoid the adverse interactions.
  
  
  METHODS
  A single dose of DCT was administered with nifedipine simultaneously, 2 h before, 30 min before or 30 min after nifedipine administration. Pharmacokinetics of nifedipine with or without DCT were compared. The influences of DCT on nifedipine intestinal mucosal and hepatic metabolism were studied by using rat in-vitro everted jejunal sac model and hepatic microsomes.
  
  
  RESULTS
  A simultaneous co-administration of DCT significantly increased the area under concentration-time curve from time zero to infinity (AUC0-inf ) of nifedipine. In-vitro mechanism investigations revealed that DCT inhibited both the intestinal and the hepatic metabolism of nifedipine. Further study on the optimal dosing interval for nifedipine and DCT revealed that administration of DCT 30 min before or after nifedipine did not significantly change the AUC of nifedipine.
  
  
  CONCLUSIONS
  The bioavailability of nifedipine is significantly increased by a simultaneous oral co-administration of DCT. This increase is caused by the inhibitory effect of DCT on both the intestinal mucosal and the hepatic metabolism of nifedipine. The dose interval between DCT and nifedipine needs to be set for over 30 min to avoid such drug-drug interactions.
authors: Institute of Natural Medicine, University of Toyama, Toyama, Japan; Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Ju-Xiu
authors: JX
authors: He
authors: Kenji
authors: K
authors: Ohno
authors: Jun
authors: J
authors: Tang
authors: Masao
authors: M
authors: Hattori
authors: Tadato
authors: T
authors: Tani
authors: Teruaki
authors: T
authors: Akao
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D017208:Rats, Wistar
chemical_list: D004365:Drugs, Chinese Herbal; C051121:daisaikoto; D009543:Nifedipine
keywords: Da-Chaihu-Tang (daisaikoto); drug-drug interaction; hepatic microsome; intestinal metabolism; nifedipine