EVALUATION OF THE DIURNAL-VARIATION IN THE PHARMACOKINETICS OF ZILEUTON IN HEALTHY-VOLUNTEERS

The diurnal variation in the pharmacokinetic parameters of zileuton we re evaluated in 12 healthy male volunteers in a three-period study. Pe riods I and II constituted a balanced, randomized, crossover study in which a participant received a single dose of 600-mg zileuton either a t 7 AM or 11 PM. In period III all participants received 600-mg doses four times daily for 5 days. The differences between the pharmacokinet ics of single doses of zileuton administered at 7 AM and at 11 PM were not statistically significant. Plasma concentration-time profiles of zileuton during the four daily dose intervals at steady state were als o similar. Values for the pharmacokinetic parameters of zileuton after multiple doses were similar to those after single doses, with a minim al accumulation of the drug after multiple doses. Overall, there was l ittle or no diurnal variation in the pharmacokinetic parameters of zil euton after single and multiple doses.