METABOLISM OF EQUILIN SULFATE IN THE DOG

The metabolism of equilin sulfate was determined in female dogs receiv ing 2.5 mg/kg of [H-3]equilin sulfate alone or in a preparation that c ontained all the components that are present in the conjugated equine estrogen product Premarin(R). The pharmacokinetic parameters of total radioactivity indicated that the drug is rapidly absorbed and it has a moderate half-life in plasma. The total radioactivity in plasma follo wing administration of [H-3]equilin sulfate as part of a mixture of co njugated equine estrogens had significantly lower peak concentration ( C-max), a lower area under the curve (AUC), a longer terminal half-lif e (t(1/2)) and a longer mean residence time (MRT) than when [H-3]equil in sulfate was given alone, indicating that the other components in th e conjugated equine estrogen preparation altered the pharmacokinetics of equilin sulfate. An average of 26.7 +/- 4.4% of the administered ra dioactive dose was excreted in urine of dogs receiving [H-3]equilin su lfate. Again, a significantly lower percentage (21.4 +/- 6.3%, P = 0.0 23) was eliminated in urine of dogs receiving [H-3]equilin sulfate in the conjugated equine estrogen preparation, indicating that the absorp tion of equilin sulfate was perhaps altered by the other components in the conjugated equine estrogen preparation. Metabolite profiles of pl asma and urine were similar. Equilin, equilenin, 17 beta-dihydroequile nin, 17 beta-dihydroequilin, 17 alpha-dihydroequilenin and 17 alpha-di hydroequilin were present in both matrices. 17 beta-Dihydroequilin and equilin were the two major chromatographic peaks in plasma samples. 1 7 beta-Dihydroequilenin and 17 beta-dihydroequilin were the major meta bolites in urine. In conclusion, following oral administration of [H-3 ]equilin sulfate to dogs, the radioactivity is rapidly absorbed. The d isposition of equilin sulfate is altered by the other components that are present in the conjugated equine estrogen preparation Premarin(R). The reduction of the 17-keto group and aromatization of ring-B are th e major metabolic pathways of equilin in the dog.