title: Excretion and stereoselective biotransformations of dl-, d- and l-norgestrel in women.
abstract: Excretion data and urinary metabolite patterns of di-, d-, and l-norgestrel were obtained from women who received a single, oral 1.5-mg dose of 14C-labeled racemic norgestrel (Ng) or one of its enantiomers. The average percentage of administered radioactivity +/- SD recovered in the urine after 7 days was 58.1 +/- 7.9% for dl-Ng, 44.8 +/- 8.9% for d-Ng, and 63.6 +/- 15.1% for l-Ng; in feces it was 23.4 +/- 7.7% (dl-Ng), 31.6 +/- 8.2% (d-Ng), and 24.8 +/- 10.7% (l-Ng). Different metabolite patterns were observed for each enantiomer in urine, and the pattern for the racemate appeared to be an approximate composite of the metabolite patterns of the two enantiomers. These differences in the metabolite pattern result from stereoselective transformations; notably 16 beta-hydroxylation of l-Ng and ring A reduction of d-Ng. Other stereoselective pathways noted were: 16 alpha- and 1 beta-hydroxylation as well as D-homoannulation of l-Ng and sulfate conjugation of l-16 beta-hydroxynorgestrel; 2 alpha-hydroxylation of d-Ng, formation of a labile neutral, polar compound which contained the norgestrel moiety in the d-form, and formation of a glucuronide of d-16 beta-hydroxynorgestre. The formation of phenolic derivatives occurred to a very minor degree from transformations of the biologically inactive l-enantiomer. With d-norgestrel, this formation occurred to an even lesser extent, if at all.
mesh_terms: D000328:Adult; D001711:Biotransformation; D005243:Feces / Q000032:analysis; D005260:Female; D005965:Glucuronates / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D009644:Norgestrel / Q000378:metabolism* / Q000652:urine; D010636:Phenols / Q000652:urine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000652:urine; D013997:Time Factors
chemical_list: D005965:Glucuronates; D010636:Phenols; D013431:Sulfates; D009644:Norgestrel