The fate of prostaglandin A1-17,18-3H in the dog

Sinha, A.J.; Shaw, S.R.

Journal of Pharmacy and Pharmacology 30(1): 51-53


ISSN/ISBN: 0022-3573
PMID: 22727
DOI: 10.1111/j.2042-7158.1978.tb13154.x
Accession: 068518277

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Peak plasma concentrations of radioactivity equivalent to 516 ng of PGA1 ml-1 were observed 5-10 s after administration of the PG, with a 2nd peak at 10-15 min after drug administration; the 2nd peak may correspond to the appearance of metabolites of PGA1 in the plasma, or the release of PGA1-3H related material from a tissue depot. The initial plasma PGA1-3H radioactivity disappearance half-life in dog was estimated to be 1 min, suggesting rapid clearance of intact PGA1. The half-life of 70 min associated with a terminal portion of the disappearance curve probably corresponds to the clearance of the metabolites of PGA1. The .beta.-oxidative cleavage of the upper carboxy side chain may be a much more important metabolic pathway than the .omega.-oxidation and .beta.-oxidative cleavage of the lower alkyl chain of PGA1. The localization of PGA1-3H radioactivity in the cellular fractions from blood samples from the PGA1-17, 18-3H treated dog was examined. Although some metabolism of the administered PGA1-3H may occur in the red blood cells, these cells did not seem to be a major site for the metabolism of this PG in the dog. After the i.v. administration of PGA1-3H to 4 dogs, urinary excretion accounted for an average of 47% of the radioactive dose. Fecal excretion similarly accounted for an average of 49% of the administered dose. Excretion of the PGA1-3H related radioactivity in the urine and feces was almost complete in 48 h after drug administration. An average of 0.5% of the radioactive dose administered was present as 3H water in the urine. An approximately equivalent fraction may be assumed to have been expired as 3H water during respiration. Both urinary and biliary excretion appear to be equally important routes for the elimination of exogenous PGA1 and related metabolites in the dog. Thus, the 3H label in PGA1-17, 18-3H is metabolically stable, and this material is suitable for use in metabolism studies in man.