title: Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer.
abstract: BACKGROUND
  Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.
  
  
  METHODS
  The pharmacokinetics of phenoxodiol was studied following a single intravenous (iv) bolus dose and during a continuous intravenous infusion. Three men with prostate cancer and 3 women with breast cancer received IV bolus phenoxodiol (5 mg/kg) and plasma was sampled for free and total phenoxodiol levels. On a separate occasion 5 of the same patients received a continuous intravenous infusion of phenoxodiol (2 mg/kg/h) and plasma was again sampled for free and total phenoxodiol levels. Phenoxodiol was measured using gradient HPLC with ultraviolet detection.
  
  
  RESULTS
  Following bolus injection, free and total phenoxodiol appeared to follow first order pharmacokinetics. The elimination half-lives for free and total phenoxodiol were 0.67 ± 0.53 h and 3.19 ± 1.93 h, respectively, while the total plasma clearance rates were 2.48 ± 2.33 L/h and 0.15 ± 0.08 L/h, respectively. The respective apparent volumes of distribution were 1.55 ± 0.69 L/kg and 0.64 ± 0.51 L/kg. During continuous intravenous infusion, free phenoxodiol accumulated rapidly to reach a mean concentration at steady state of 0.79 ± 0.14 μg/ml after 0.87 ± 0.18 h. The apparent accumulation half-life of free phenoxodiol was 0.17 ± 0.04 h while the plasma clearance during continuous infusion was 1.29 ± 0.23 L/h.
  
  
  CONCLUSIONS
  Phenoxodiol has a short plasma half-life, particularly in the free form, leading to a rapid attainment of steady state levels during continuous intravenous infusion.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12610000334000.
authors.affiliation: Department of Pharmacology and Therapeutics, Griffith University, Gold Coast Hospital, Southport, Queensland, Australia.
authors.forename: Jan B
authors.initials: JB
authors.lastname: Howes
authors.forename: Paul L
authors.initials: PL
authors.lastname: de Souza
authors.forename: Leanne
authors.initials: L
authors.lastname: West
authors.forename: Li Jiu
authors.initials: LJ
authors.lastname: Huang
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Howes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001315:Australia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007529:Isoflavones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007529:Isoflavones; C471183:phenoxodiol