Further studies of the acute effects of phenylbutazone, oxyphenbutazone and indomethacin on the rat kidney.

Experiments were donducted on rats to determine the lowest dose of either phenylbutazone or indomethacin capable of producing papillary necrosis and in each case it was found to be 50 mg/kg body weight. A single dose of oxyphenbutazone (444 mg/kg), a major metabolite of phenylbutazone in man, produced patchy cortical necrosis, which became more extensive during daily administration for 4 days, despite evidence of regeneration. Although papillary necrosis as such was never seen with this substance, there was evidence of damage to the lower nephron in the form of tubular necrosis and calcification.