Absolute bioavailability and metabolism of aceclofenac in rats

Aceclofenac is one of the most popular analgesic and anti-inflammatory drugs used for the relief of pain, rheumatoid arthritis, and osteoarthritis. To date, no intravenous preparation of aceclofenac has been developed because of its poor water solubility. In this study, to investigate its absolute bioavailability and metabolism in rats, aceclofenac was dissolved in a sterile aqueous solution containing urea (20 %) and trisodium citrate (10 %), and administered via oral (20 mg/kg) and intravenous (10 mg/kg) routes. Blood samples were taken serially, and aceclofenac and its three major metabolites (4′-hydroxydiclofenac, 4′-hydroxyaceclofenac, and diclofenac) were measured by HPLC–MS/MS. The absolute oral bioavailability of aceclofenac was approximately 15 %. Diclofenac and 4′-hydroxydiclofenac were the main metabolites in rats, in contrast to 4′-hydroxyaceclofenac in humans. The low bioavailability of aceclofenac is likely due to extensive metabolism, and bioavailability may be even lower if the drug were administered as a tablet, considering its low water solubility. This study provides complete time profiles of the plasma concentrations of aceclofenac and its metabolites in rats and highlights the difference in drug metabolism between rats and humans.