Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey
The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C was cortisol during the 40-min period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the /sup 3/H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6.
- Research Organization:
- Division of Teratogenesis Research, National Center for Toxicological Research, Food and Drug Administration, Davis, California
- OSTI ID:
- 6623014
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 223:2
- Country of Publication:
- United States
- Language:
- English
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TRACER TECHNIQUES
HYDROCORTISONE
METABOLISM
PHARMACOLOGY
PREDNISOLONE
TRITIUM COMPOUNDS
BIOCHEMICAL REACTION KINETICS
FETUSES
MACACUS
PLACENTA
PREGNANCY
ADRENAL HORMONES
ANIMALS
CORTICOSTEROIDS
FETAL MEMBRANES
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HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
MONKEYS
ORGANIC COMPOUNDS
PREGNANES
PRIMATES
REACTION KINETICS
STEROID HORMONES
STEROIDS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
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