Summary
The pharmacokinetics and pharmacodynamics of zileuton were determined after oral administration of single dose (600mg) and multiple dose regimens [600mg every 8 hours (q8h regimen) and 600mg every 6 hours (q6h regimen)] in 12 healthy male subjects aged 18 to 50 years. Steady-state peak plasma concentration (Cmax), time to Cmax, apparent total plasma clearance, and apparent terminal phase volume of distribution values after the q8h and q6h regimens were 3.07 ± 1.13 and 4.37 ± 1.02 mg/L, 1.5 ±0.9 and 1.5 ±0.9 hours, 793 ± 233 and 579 ± 162 ml/min (47.6 and 34.7 L/h), and 179 ± 126 and 115 ± 29L, respectively (mean ± SD). Trough zileuton plasma concentrations (Cmin) immeiately before the morning dose were higher than Cmin immediately before the afternoon dose, suggesting a diurnal variation in the pharmacokinetics of zileuton. Accumulation of zileuton occurred with more frequent dose administration, although there was no unexpected accumulation of the parent drug or the N-dehydroxyzileuton metabolite. The q6h regimen of zileuton 600mg was superior to the q8h regimen in maintaining trough plasma concentrations of zileuton above 1.5 mg/L, corresponding to approximately 70 to 80% inhibition of leukotriene B4 biosynthesis.
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Awni, W.M., Braeckman, R.A., Granneman, G.R. et al. Pharmacokinetics and Pharmacodynamics of Zileuton after Oral Administration of Single and Multiple Dose Regimens of Zileuton 600mg in Healthy Volunteers. Clin-Pharmacokinet 29 (Suppl 2), 22–33 (1995). https://doi.org/10.2165/00003088-199500292-00005
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DOI: https://doi.org/10.2165/00003088-199500292-00005