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The metabolism of mestranol, ethynylestradiol, norethynodrel, norethindrone, ethynodiol diacetate, lynestrenol, and norgestrel is reviewed. The estrogenic components of the oral contraceptives, mestranol or ethynylestradiol, have nearly identical metabolic pathways since mestranol is rapidly and almost completely converted to ethynylestradiol The major fraction of the drugs plus metabolites is excreted in the urine as conjugated materials. All of the 17beta-ethynyl progestins reviewed follow similar metabolic paths. For three of these, norethynodrel, ethynodiol diacetate and lynestrenol, a principal metabolite is norethindrone. Biotransformation to more polar metabolites and conjugation proceed rapidly for these three precursor drugs and norethindrone. Norgestrel follows metabolic paths similar to those of norethindrone. However, the ethyl moiety at the C-13 position appears to slow the metabolism of this steroid so that biotransformation to more polar metabolites and the conjugation of these steroids does not proceed as rapidly as that of the other progestins. The high progestational potency of norgestrel may be attributed to this slow rate of biotransformation. Some of the pharmacokinetic parameters derived from the research reports reviewed here are summarized. The compounds appear to be readily absorbed, and they and their metabolites are excreted to a greater extent in the urine than in the feces.

Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid, methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening agent that organoleptically has about 180 times the sweetness of sugar. The metabolism of aspartame has been studied in mice, rats, rabbits, dogs, monkeys, and humans. The compound was digested in all species in the same way as are natural constituents of the diet. Hydrolysis of the methyl group by intestinal esterases yielded methanol, which was oxidized in the one-carbon metabolic pool to CO2. The resultant dipeptide was split at the mucosal surface by dipeptidases and the free amino acids were absorbed. The aspartic acid moiety was transformed in large part to CO2 through its entry into the tricarboxylic acid cycle. Phenylalanine was primarily incorporated into body protein either unchanged or as its major metabolite, tyrosine.

Aspartame (3-amino-N-(alpha-carboxyphenethyl) succinamic acid, methyl ester; the methyl ester of aspartylphenylalanine, SC-18862) is hydrolyzed in the gut to yield aspartic acid, phenylalanine, and methanol. This review of the literature describes the metabolic paths followed by aspartate in its conversion to CO2 or its incorporation into body constituents. About 70 percent of 14C from [asp-14C]-aspartame is converted in the monkey to 14CO2. Some of the aspartate is converted at the intestinal mucosal level to alanine by decarboxylation. This amino acid may be oxidized to CO2 by entering the tricarboxylic acid cycle via pyruvate and acetyl CoA. In addition, transamination of aspartate to oxaloacetate permits this product also to enter the tricarboxylic acid cycle. Aspartate may also be incorporated into body constitutents such as other amino acids, proteins, pyrimidines, asparagine, and N-acetylaspartic acid. It is concluded that the aspartate moiety of aspartame is metabolized in a manner similar to that of dietary aspartic acid.

Chemical and histochemical analyses were carried out on uteri of four monkeys in which plastic IUDs or Cu-IUDs had been implanted for 36 to 43 days. The mean uterine copper content of the plastic-treated animals was 1.1 mug/gm (mean of two), while this value for the Cu-IUD treated monkeys was 1.7 mug/gm. The copper was distributed primarily in the cyclically renewed regions of the endometrium: the luminal fluid, endometrial surface, and superficial lamina propria. The element was localized and was not uniformly distributed in these regions. Copper analyses of plasma, liver, and kidney showed no differences between these two groups. Histopathologic evaluation revealed some areas of edema and increased numbers of neutrophils in plastic-IUD-treated animals. In the Cu-IUD-implanted monkeys, similar changes were observed as was a flattening of the surface epithelium. The endometrium had a loose areolar appearance. The copper elution rate was about 90 mug/day, about twice that observed in women using Cu-IUDs.