The effect of zileuton on antipyrine and indocyanine green disposition

Clin Pharmacol Ther. 1995 Mar;57(3):299-308. doi: 10.1016/0009-9236(95)90155-8.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antipyrine / blood
  • Antipyrine / pharmacokinetics*
  • Antipyrine / urine
  • Double-Blind Method
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / analogs & derivatives*
  • Hydroxyurea / pharmacology
  • Indocyanine Green / pharmacokinetics*
  • Lipoxygenase Inhibitors / administration & dosage
  • Lipoxygenase Inhibitors / pharmacology*
  • Male

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipoxygenase Inhibitors
  • Indocyanine Green
  • Antipyrine
  • zileuton
  • Hydroxyurea