Metabolism and pharmacokinetics of progesterone in the cynomolgus monkey (Macaca fascicularis).
[4-14C]Progesterone was administered to two cycling female monkeys during the luteal phase of the cycle, and blood and urine were sampled over a 24 h period. Progesterone had a volume of distribution of 1.75 +/- 0.3 L/kg, and a plasma elimination clearance of 0.06 +/- 0.03 L/kg/min. In comparison to the human, plasma progesterone binding was greater and progesterone clearance was slower in the cynomolgus monkey. The major unconjugated metabolite in plasma was 20 alpha-hydroxy-4-pregnen-3-one. In urine 6.2% of 14C-steroids were unconjugated, 2.3% of which were [14C]progesterone. Thin-layer chromatography (TLC) of conjugated metabolites in urine revealed that 24% had the mobility of sulfates, 19% that of glucuronides, and 52% were more polar. After hydrolysis of conjugates, a major fraction chromatographed with pregnanediol. However, despite evidence for the presence of a 20 alpha-hydroxyl group, none of the pregnanediol isomers could be identified among these 14C-steroids. Nevertheless, over 80% of urinary metabolites had sufficient analogy to pregnanediol to bind to an antiserum specific for ring D and the C-17 side-chain of pregnanediol.
Braasch
H V
HV
Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, IL 60611.
Frederiksen
M C
MC
Chatterton
R T
RT
D000818:Animals; D002855:Chromatography, Thin Layer; D004970:Estrone / Q000652:urine; D005260:Female; D008183:Luteal Phase; D008251:Macaca / Q000378:metabolism*; D008252:Macaca fascicularis / Q000378:metabolism*; D011276:Pregnanediol / Q000652:urine; D011374:Progesterone / Q000378:metabolism* / Q000493:pharmacokinetics
D004970:Estrone; D011374:Progesterone; D011276:Pregnanediol