THE EFFECT OF ZILEUTON ON ANTIPYRINE AND INDOCYANINE GREEN DISPOSITION

The effects of single and multiple oral doses of zileuton on the pharm acokinetics of antipyrine and indocyanine green were studied in 16 hea lthy, nonsmoking adult men by means of a double-blind, randomized, par allel placebo-controlled design. Indocyanine green disposition was not significantly altered by zileuton. Plasma antipyrine clearance declin ed by 20% (p < 0.0005) and 52% (p < 0.0005) after single and multiple dose zileuton exposure, respectively Total urinary recovery of unchang ed antipyrine and metabolites decreased with zileuton exposure. Select ive declines from baseline of 16% (p = 0.007) and 20% (p = 0.003) afte r single-dose zileuton and 30% (p < 0.0005) and 43% (p < 0.0005) after multiple-dose zileuton were detected in recovery of 4-hydroxyantipyri ne and 3-hydroxymethylantipyrine, respectively. Urinary recovery of th e N-demethylantipyrine metabolite norantipyrine and percent of conjuga tion of 3-hydroxymethylantipyrine were unchanged by zileuton. In concl usion, zileuton therapy has no detectable effect on indocyanine green disposition but exerts marked effects on antipyrine plasma and urine m etabolite disposition.