Metabolism and pharmacokinetics of progesterone in the cynomolgus monkey (Macaca fascicularis)

Heidi V. Braasch, Marilynn C. Frederiksen, Robert Treat Chatterton Jr*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

[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 20α-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 20α-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.

Original languageEnglish (US)
Pages (from-to)279-294
Number of pages16
JournalSteroids
Volume52
Issue number3
DOIs
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Pharmacology
  • Endocrinology
  • Clinical Biochemistry
  • Organic Chemistry

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