Printed in L’.S.A. SULFAMETHAZINE AS A MODEL COMPOUND TO ASSESS SEX HORMONE-DEPENDENT CYTOCHROME P-450 ACTIVITY IN RATS (original) (raw)

1992

Abstract

Plasma disposition and urinary recovery of sulfamethazine (SMZ), its N4-acetylated metabolite (N4AcSMZ), and two of its hydroxylated metabolites [5-hydroxysulfamethazine (5OHSMZ) and 6-hydroxy-methylsulfamethazine (6CH2OHSMZ)J were determined in male and female rats, in castrated males, and in rats pretreated with various steroid hormones. Male rats had a 2-fold higher SMZ plasma clear-ance than females, castrates, and males treated with flutamide (a testosterone antagonist). When castrated male rats were treated with testosterone or trenbolone, SMZ plasma clearance returned to normal values. Higher SMZ plasma clearance rates in the presence of androgens went together with higher urinary recoveries of the 6CH2OHSMZ metabolite. In hepatic microsomes of male rats lower apparent KM values, and higher values for 6CH2OHSMZ and 5OHSMZ formation were found than in microsomes of female rats. Castration or treatment of male rats with flutamide markedly reduced

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