Disposition and enterohepatic circulation of diclofenac in dogs

Arzneimittelforschung. 1980;30(10):1650-3.

Abstract

Following i.v. administration of 14C-labelled 2-(2',6'-dichloroanilino) phenylacetic acid (14C-diclofenac) (25 mg/kg) to dogs, 65% of the dose of total radioactivity was excreted in the bile in the first 6 h. A trace of unchanged diclofenac and three metabolites were demonstrated in the bile by 2-dimensional TLC. Two of these metabolites were identified as diclofenac acyl-glucuronide (80% of total radioactivity in the bile) and taurine conjugate (10%); the third was an unknown metabolite (2%). Diclofenac acyl-glucuronide was hydrolyzed by weak alkaline and beta-glucuronidase. Intraduodenally administered diclofenac acyl-glucuronide was absorbed, and then excreted in the bile again. This suggests that diclofenac acyl-glucuronide is hydrolyzed in the intestine, and undergoes enterohepatic circulation. The plasma half-life of diclofenac was 1.3 h in dogs.

MeSH terms

  • Animals
  • Biotransformation
  • Diclofenac / metabolism*
  • Dogs
  • Drug Stability
  • Enterohepatic Circulation
  • Female
  • Male
  • Phenylacetates / metabolism*

Substances

  • Phenylacetates
  • Diclofenac