TISSUE DISTRIBUTION AND BILIARY-EXCRETION OF PROSTACYCLIN METABOLITES IN THE RAT

  • 1 January 1980
    • journal article
    • research article
    • Vol. 214  (1) , 24-30
Abstract
When 3H labeled prostacyclin (PGI2) or 6-keto PG[prostaglandin]F1.alpha. were injected i.v. into rats, 1/3 of the dose appeared in the liver after 15 min. Significant levels of radioactivity (8-16%) were found in the small intestine. These observations plus the prominant fecal excretion of PGI2 radioactivity suggest that PGI2 and/or its metabolites undergo biliary excretion and enterohepatic recirculation. PGI2 excretion and metabolite composition of the bile was studied in bile duct cannulated rats. After a single bolus i.v. injection of 11-[3H] PGI2 into these rats, an average of 37% of the administered radioactivity was excreted in the bile within 3 h. A number of metabolites were detected in the bile. The major metabolites were isolated and identified as 2,3-dinor-6-keto-PGF1.alpha. and 13,14-dihydro-2,3-dinor-6,15-diketo-PGF1.alpha.-glucuronide which each accounted for .apprx. 1/3 of the radioactivity in the bile. Other metabolites include 6-keto PGF1.alpha., 13,14-dihydro-2,3-dinor-6,15-diketo-PGF1.alpha., 13,14-dihydro-2,3-dinor-6,15-diketo-20-carboxyl PGF1.alpha. and 2,3,4,5,6-pentanor-PGF1.alpha.-.gamma.-lactone. The liver plays a pivotal role in the inactivation and disposition of PGI2. The predominate metabolic pathways occurring in the liver are probably .beta.-oxidation and glucuronic acid conjugation.