In Vivo Inhibition of Prostaglandin Synthesis in Rabbit Kidney by Non‐Steroidal Anti‐Inflammatory Drugs

Abstract

To define dose- and time-response properties for in vivo inhibition of renal prostaglandin (PG) synthesis, aspirin, diclofenac sodium, indomethacin and d-naproxen were injected intravenously in different doses to unanaesthetized rabbits. After 30 min. the animals were killed and the post mortem accumulation of PGE₂ and PGF_2α in the renal medulla was determined by mass fragmentography. In control animals, the accumulated levels of PGE₂ and PGF_2α in the medulla were 9.2±2.2 (S.D.) and 1.5 ± 0.6 μg/g, respectively. Dose-dependent inhibition was demonstrated with all the drugs. The ED95 was for aspirin 15 mg/kg, for diclofenac sodium 1.5 mg/kg, for indomethacin 1.5 mg/kg and for d-naproxen 5 mg/kg. The duration of inhibition was studied by radioimmunoassay in anaesthetized rabbits by following the urinary excretion of PGF_2α and PGE₂ after an intravenous injection of solvent or test drug in doses twice the ED95. For three hours following aspirin, diclofenac sodium, indomethacin and d-naproxen, the decreases in urinary excretion of PGF_2α ranged from 64 to 88, 87 to 95, 64 to 90 and from 40 to 77 per cent of the control, respectively, and the decreases in PGE₂ excretion were of similar magnitude. Together these results indicate that diclofenac sodium might be used as a long-lasting and potent alternative to indomethacin and aspirin in experimental studies on the renal PG system in vivo.