title: [Dose-dependent pharmacokinetic study of genistein in Beagle dogs].
abstract: OBJECTIVE
  To study the pharmacokinetics of genistein at different doses in Beagle dogs.
  
  
  METHODS
  Suspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software.
  
  
  RESULTS
  The plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively.
  
  
  CONCLUSIONS
  Due to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.
authors.affiliation: Department of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Zhou
authors.forename: Qi-Bing
authors.initials: QB
authors.lastname: Mei
authors.forename: Ru-Tao
authors.initials: RT
authors.lastname: Wang
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Wang
authors.forename: Zhi-Fu
authors.initials: ZF
authors.lastname: Yang
authors.forename: Si-Wang
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D020719:Glucuronides / Q000097:blood / Q000493:pharmacokinetics; D008297:Male
chemical_list: D016588:Anticarcinogenic Agents; D020719:Glucuronides; D019833:Genistein