The effect of mild or moderate hepatic impairment (cirrhosis) on the pharmacokinetics of zileuton.
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.
Awni
W M
WM
Pharmacokinetics and Biopharmaceutics Department, Abbott Laboratories, Abbott Park, Illinois, USA.
Cavanaugh
J H
JH
Braeckman
R A
RA
Chu
S Y
SY
Patterson
K J
KJ
Machinist
J M
JM
Granneman
G R
GR
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
D001798:Blood Proteins; D005965:Glucuronates; D016859:Lipoxygenase Inhibitors; C063449:zileuton; D006918:Hydroxyurea