Effect of sex hormones on the disposition in rats of 1-aminocyclohexane carboxylic acid, a metabolite of semisynthetic penicillin.

The renal clearance of 1-aminocyclohexanecarboxylic acid (ACHC), a metabolite of the semisynthetic penicillin, cyclacillin, is about 10 times faster in female than in male rats. The slower clearance in males is attributed to a higher net rate of reabsorption of the compound from the tubule of the kidney. Because ACHC is not metabolized, it is apparently continuously recirculated through the kidney of the male, resulting in the longer half-life. The sex-related disposition of the metabolite can be modified by gonadectomy and/or treatment with sex hormones. Castrated males show increased urinary excretion and decreased plasma half-life of ACHC relative to intact males. In ovariectomized females, less ACHC is excreted and the half-life is longer than in intact females. Thus, in both sexes, gonadectomy shifts the excretion and the residence time in plasma toward the values of these parameters for the opposite sex. Treatment of castrated males with estradiol markedly enhances the effect of castration, but treatment of ovariectomized females with testosterone propionate has little or no additional effect over ovariectomy. Treatment of intact males with estradiol modifies both excretion and residence time in plasma to a great extent, but treatment of intact females with testosterone has a lesser effect on the disposition of ACHC. These results indicate that excretion and residence time of ACHC in both male and female rats are influenced by sex hormones. The described effect is an example of the action of sex hormones on the transport of foreign compounds in this species. Its mechanism is quite different from the well known influence of sex hormones on the microsomal metabolism of foreign compounds in rats.