The Metabolism of Ibuprofen

Abstract

1. After oral administration ibuprofen appeared mainly in unchanged form in the plasma of rats, dogs, baboons and men. It disappeared more slowly from the plasma of dogs than from that of other species. On repeated dosing it accumulated most in dog plasma.

2. Two metabolites, 2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid (metabolite A) and 2-[4-(2-carboxypropyl)phenyl]propionic acid (metabolite B), were found in rat, baboon and human plasma, but not in dog plasma. Both metabolites were found in the urines of all four species, but there were marked differences in proportions and extent of conjugation.

3. Rats excreted in bile about 28% of a single intravenous dose of [¹⁴C]ibu-profen in 3 hours and a dog excreted 25% in the same period. Biliary cannulation did not influence plasma radioactivity, suggesting that little enterohepatic circulation occurred.

4. At clinically significant concentrations ibuprofen was strongly bound to plasma protein in vitro, 95% being bound in baboon, 96% in rat, and 99% in dog and human plasma.

5. After administration of either (+) or (-)-ibuprofen to man, urinary metabolites A and B were dextrorotatory.

6. In the rat ibuprofen induced neither its own metabolism nor that of sodium pentobarbitone, but sodium pentobarbitone induced the metabolism of ibuprofen.