title: The effect of mild or moderate hepatic impairment (cirrhosis) on the pharmacokinetics of zileuton.
abstract: The pharmacokinetics of zileuton and its R(+) and S(-) glucuronide metabolites were determined after single and multiple (400mg every 8 hours) oral dose administration in healthy subjects (n = 5) and patients with mild or moderate hepatic impairment (cirrhosis; n = 8). The clearance of total zileuton (unbound plus bound to plasma proteins) in patients with hepatic impairment (approximately 350 ml/min) was approximately half than in healthy subjects (approximately 670 ml/min), with similar values in patients with mild or moderate cirrhosis. However, the clearance of unbound zileuton in patients with moderate hepatic impairment was nearly half that in patients with mild hepatic impairment, and one quarter that in healthy subjects. On the basis of these findings, it may be necessary to reduce the dose in patients with impaired hepatic function to maintain levels similar to those in healthy subjects.
authors.affiliation: Pharmacokinetics and Biopharmaceutics Department, Abbott Laboratories, Abbott Park, Illinois, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Awni
authors.forename: J H
authors.initials: JH
authors.lastname: Cavanaugh
authors.forename: R A
authors.initials: RA
authors.lastname: Braeckman
authors.forename: S Y
authors.initials: SY
authors.lastname: Chu
authors.forename: K J
authors.initials: KJ
authors.lastname: Patterson
authors.forename: J M
authors.initials: JM
authors.lastname: Machinist
authors.forename: G R
authors.initials: GR
authors.lastname: Granneman
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000375:Aging / Q000097:blood / Q000652:urine; D001798:Blood Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005965:Glucuronates / Q000652:urine; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D005965:Glucuronates; D016859:Lipoxygenase Inhibitors; C063449:zileuton; D006918:Hydroxyurea