PHARMACOKINETICS OF ZILEUTON AND ITS METABOLITES IN PATIENTS WITH RENAL IMPAIRMENT

The pharmacokinetics of zileuton and its conjugated metabolites were e valuated in patients with chronic renal impairment. Five healthy volun teers (creatinine clearance > 90 mL/min), five patients with renal fai lure requiring hemodialysis, six with mild (creatinine clearance, 60-9 0 mL/min), eight with moderate (creatinine clearance, 30-59 mL/min), a nd six with severe (creatinine clearance < 30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all partici pants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in health y volunteers; in patients with mild, moderate and severe renal impairm ent; and in patients with renal failure requiring hemodialysis. The me an metabolite/parent-area ratios for the pharmacologically inactive zi leuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (< 0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure re quiring hemodialysis.