title: Effect of gonadectomy and hormones on sex differences in ketoprofen enantiomer glucuronidation and renal excretion of formed glucuronides in the rat.
abstract: OBJECTIVE
  To investigate the sex hormone dependency of phase II metabolism using S-ketoprofen (S-KT) urinary excretion (sigmaXu) as a marker in the rat.
  
  
  METHODS
  The effect of surgical gonadectomy, with or without concomitant estradiol or testosterone treatment, on the sigmaXu of glucuronidated S-KT was studied in male and female rats. Hepatic and renal glucuronidation of KT enantiomers was also determined using microsomal preparations from these animals.
  
  
  RESULTS
  A controlling effect of testosterone was demonstrated by a rapid increase in sigmaXu of glucuronidated S-KT in castrated males (27.9 +/- 9.0%) compared to control males (7.2 +/- 3.9%). This approximated control female excretion (40.5 +/- 11.6%). Treatment of ovarectomized females with testosterone resulted in a steady reduction in sigmaXu of glucuronidated S-KT with time (13.4 +/- 5.4% at end point). Hepatic glucuronidation of S-KT by male rat liver microsomes was significantly higher than that of female, whereas renal glucuronidation of S-KT by female rat kidney microsomes was significantly higher than that of male. Significant correlations were found between hepatic (r = -0.78) or renal (r = 0.83) glucuronidation and sigmaXu of glucuronidated S-KT.
  
  
  CONCLUSIONS
  Urinary excretion of S-KT-GC is sex hormone-dependent. This metabolite may have utility as a marker or probe for sex hormone-dependent studies of phase II metabolism.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
authors.forename: Eugenia L
authors.initials: EL
authors.lastname: Palylyk-Colwell
authors.forename: Fakhreddin
authors.initials: F
authors.lastname: Jamali
mesh_terms: D000818:Animals; D002170:Canada; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005544:Forecasting; D005965:Glucuronates / Q000652:urine*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D007660:Ketoprofen / Q000494:pharmacology / Q000652:urine*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013237:Stereoisomerism; D013739:Testosterone / Q000494:pharmacology
chemical_list: D005965:Glucuronates; D012739:Gonadal Steroid Hormones; D013739:Testosterone; D004958:Estradiol; D007660:Ketoprofen