Dose‐dependent enzyme induction

Abstract

Administration of qUinalbarbitone, 100 mg nightly, caused a fall in steady‐state plasma warfarin concentration ranging from 5% to 64.5% in 6 patients. There was no correlation between the extent of this fall and either the plasma concentration of quinalbarbitone or the initial rate of warfarin metabolism. Increasing the dose of qUinalbarbitone to 200 mg nightly (2 patients) and 300 mg nightly (1 patient) permitted a study of the relationship between dose and degree of induction. By administration of varying doses of 4 inducing agents to rats and constructing a dose‐response curve, it was shown that phenobarbitone was a more potent inducing agent than quinalbarbitone, amylobarbitone, or antipyrine. Possible reasons for this include the longer plasma half‐life of phenobarbitone and the higher liver/plasma drug ratio. These data suggest that more information about the indUCing ability of drugs in man and animals can be derived by performing enzyme induction studies at several rather than at a single dose level.