title: Enantiospecific pharmacokinetics of isoxanthohumol and its metabolite 8-prenylnaringenin in the rat.
abstract: METHODS
  Isoxanthohumol (IX) is a bioactive dietary prenylflavanone found in hops (Humulus lupulus L.), beer and nutraceuticals. IX is formed in vivo by xanthohumol and is a prodrug of 8-prenylnaringenin (8PN). IX and 8PN chirality has largely been ignored in the literature due to lack of enantiospecific bioanalytical methods. No single dose pharmacokinetic study of IX exists in the literature for any species. This study elucidates the enantiospecific pharmacokinetics of IX in rats and monitors the appearance of 8PN following intravenous and oral administration of ±IX.
  
  
  RESULTS
  After intravenous (10 mg/kg) or oral (100 mg/kg) administration of ±IX to rats, serum, and urine were collected for 120 h and analyzed for IX and 8PN. Both were found as aglycones and glucuronide conjugates and displayed multiple peaking in serum suggestive of enterohepatic recycling. IX is primarily excreted through nonrenal routes. S-8PN was found excreted in the urine in greater amounts than R-8PN. Bioavailability was determined to be ∼4-5% for IX.
  
  
  CONCLUSIONS
  Further enantiospecific pharmacokinetics of IX, subsequent 8PN and other metabolites are warranted along with continued enantiospecific bioactivity studies, especially in relation to gut microbial metabolism of IX and subsequent formation of 8PN.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Martinez
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Neal M
authors.initials: NM
authors.lastname: Davies
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002942:Circular Dichroism; D019587:Dietary Supplements; D044950:Flavanones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D020719:Glucuronides / Q000097:blood; D027582:Humulus / Q000737:chemistry; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D044004:Xanthones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: C119737:8-prenylnaringenin; D044950:Flavanones; D020719:Glucuronides; D010936:Plant Extracts; D044004:Xanthones; C512910:isoxanthohumol
keywords: Chiral; Flavonoids; Isoxanthohumol; LC-MS; Pharmacokinetics