title: [Effects of Shenmai Injection on serum concentration and pharmacokinetics of digoxin in dogs with heart failure].
abstract: OBJECTIVE
  To explore the effects of Shenmai Injection (SMI), a compound traditional Chinese herbal medicine, on pharmacokinetics and serum concentration of digoxin when applied together with digoxin.
  
  
  METHODS
  Twenty dogs with heart failure were randomly divided into 4 groups: control group and low-, medium- and high-dose SMI groups, with 5 dogs in each group. After intravenous injection of digoxin injection at a dose of 7.41 μg/kg, dogs in the control group were administered intravenously with normal saline 20 mL daily for 5 d, and the other groups were intravenously administered with SMI at the doses of 0.517, 1.034 and 1.551 mL/kg respectively. After the administration, the blood was collected at designed time points. Serum concentration of digoxin was determined by high-performance liquid chromatography with electrospray tandem mass spectrometry (HPLC/MS/MS).
  
  
  RESULTS
  The low-, medium- and high-dose SMI showed different effects on the pharmacokinetics of digoxin: the low-, medium- and high-dose SMI revealed a tendency to decrease the elimination half-life (T(1/2β)) of digoxin. The low-dose SMI showed a tendency to decrease the digoxin concentration. Serum clearance (CL) in the low-dose SMI group was higher than that in the control, and also significantly higher than those in the medium- and high-dose SMI groups (P<0.05). The area under concentration-time curve (AUC(0→∞)) in the low-dose SMI group was lower than that in the control group (P=0.05); the AUC(0→72 h) and AUC(0→∞) in the low-dose SMI group were significantly lower than those in the medium- and high-dose SMI groups. Low-dose SMI accelerated the clearance of digoxin in blood.
  
  
  CONCLUSIONS
  Low-, medium- and high-dose SMI shows different effects on pharmacokinetics of digoxin and reveals a tendency to shorten T(1/2β) of digoxin. Low-dose SMI can accelerate the clearance of digoxin in blood.
authors.affiliation: Department of Cardiology, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. jymao@126.com
authors.forename: Jing-yuan
authors.initials: JY
authors.lastname: Mao
authors.forename: Chang-xiao
authors.initials: CX
authors.lastname: Liu
authors.forename: Heng-he
authors.initials: HH
authors.lastname: Wang
authors.forename: Guang-li
authors.initials: GL
authors.lastname: Wei
authors.forename: Zhen-peng
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Xing
authors.forename: Xian-liang
authors.initials: XL
authors.lastname: Wang
authors.forename: Ying-fei
authors.initials: YF
authors.lastname: Bi
mesh_terms: D000818:Animals; D004077:Digoxin / Q000097:blood* / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004285:Dogs; D004338:Drug Combinations; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006333:Heart Failure / Q000097:blood*; D007267:Injections
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D004077:Digoxin