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  • Title: Effect of gonadectomy and hormones on sex differences in ketoprofen enantiomer glucuronidation and renal excretion of formed glucuronides in the rat.
    Author: Palylyk-Colwell EL, Jamali F.
    Journal: Pharm Res; 2004 Jun; 21(6):989-95. PubMed ID: 15212164.
    Abstract:
    PURPOSE: 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.
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