TY - JOUR
T1 - Metabolism and pharmacokinetics of progesterone in the cynomolgus monkey (Macaca fascicularis)
AU - Braasch, Heidi V.
AU - Frederiksen, Marilynn C.
AU - Chatterton Jr, Robert Treat
PY - 1988/1/1
Y1 - 1988/1/1
N2 - [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.
AB - [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.
UR - http://www.scopus.com/inward/record.url?scp=0024211481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024211481&partnerID=8YFLogxK
U2 - 10.1016/0039-128X(88)90009-8
DO - 10.1016/0039-128X(88)90009-8
M3 - Article
C2 - 3254628
AN - SCOPUS:0024211481
VL - 52
SP - 279
EP - 294
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 3
ER -