The effect of zileuton on antipyrine and indocyanine green disposition.
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.
St Peter
J V
JV
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, MN 55404-1249, USA.
Braeckman
R A
RA
Granneman
G R
GR
Locke
C S
CS
Cavanaugh
J H
JH
Awni
W M
WM
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D007208:Indocyanine Green; D000983:Antipyrine; C063449:zileuton; D006918:Hydroxyurea