Circadian variations of phenacetin metabolism in rats in vivo and in vitro.

Abstract

The metabolism of phenacetin in vivo and in vitro at different periods of day was investigated in rats. In rats maintained on standard LD conditions the disappearance rate of phenacetin from blood and activity of phenacetin O-deethylase in liver were the highest in the morning and the lowest in the evening. Continuous illumination, adrenalectomy, phenobarbital or proadifen abolished this difference. It is postulated that these circadian changes of microsomal metabolism of phenacetin in rats liver are not fully responsible for the rhythmical changes in the antipyretic action of this drug that was observed previously. The mechanisms of this phenomenon are discussed.