title: The effect of zileuton on antipyrine and indocyanine green disposition.
abstract: The effects of single and multiple oral doses of zileuton on the pharmacokinetics of antipyrine and indocyanine green were studied in 16 healthy, nonsmoking adult men by means of a double-blind, randomized, parallel placebo-controlled design. Indocyanine green disposition was not significantly altered by zileuton. Plasma antipyrine clearance declined by 20% (p < 0.0005) and 52% (p < 0.0005) after single and multiple dose zileuton exposure, respectively. Total urinary recovery of unchanged antipyrine and metabolites decreased with zileuton exposure. Selective declines from baseline of 16% (p = 0.007) and 20% (p = 0.003) after single-dose zileuton and 30% (p < 0.0005) and 43% (p < 0.0005) after multiple-dose zileuton were detected in recovery of 4-hydroxyantipyrine and 3-hydroxymethylantipyrine, respectively. Urinary recovery of the N-demethylantipyrine metabolite norantipyrine and percent of conjugation of 3-hydroxymethylantipyrine were unchanged by zileuton. In conclusion, zileuton therapy has no detectable effect on indocyanine green disposition but exerts marked effects on antipyrine plasma and urine metabolite disposition.
authors.affiliation: Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, MN 55404-1249, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: St Peter
authors.forename: R A
authors.initials: RA
authors.lastname: Braeckman
authors.forename: G R
authors.initials: GR
authors.lastname: Granneman
authors.forename: C S
authors.initials: CS
authors.lastname: Locke
authors.forename: J H
authors.initials: JH
authors.lastname: Cavanaugh
authors.forename: W M
authors.initials: WM
authors.lastname: Awni
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004311:Double-Blind Method; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D007208:Indocyanine Green; D000983:Antipyrine; C063449:zileuton; D006918:Hydroxyurea