Chronopharmacological studies of phenylbutazone in the rat

Temporal variations in the anti-inflammatory action and in the ulcerogenic and lethal effects of phenylbutazone were studied in rats. The results indicate that small doses of the drug produced a larger reduction of paw edema in the morning than in the evening. At 0900, doses of 10, 30, and 100 mg/kg of phenylbutazone reduced the carrageenan-induced paw edema by 23, 44, and 66%, respectively. At 2000, the same doses of the drug decreased the paw edema by 9, 22, and 62%, respectively. No circadian variation was observed in the ulcerogenic effect of phenylbutazone. The mean lethal dose (LD50) of the drug was larger in the morning than in the evening and the values obtained were 710 +/- 24 (SE) mg/kg at 0900 in comparison to 525 +/- 38 (SE) mg/kg at 2000.