Metabolism of leukotriene B₄ in the monkey. Identification of the principal nonvolatile metabolite in the urine

Five milligrams of [5,6,8,9,11,12,14,15-³H₈]-leukotriene B₄ (LTB₄) (1.68 Ci/mmol) were infused into a monkey over a three hour period. Twenty-five per cent of the infused ³H-activity was recovered in the urine during the twenty hours of collection. Plasma and urinary metabolite volatility studies revealed that in contrast to previously studied eicosanoids, more than 70% per cent of the infused LTB₄ ³H-label was converted to tritiated water. The major nonvolatile urinary metabolite of LTB₄ representing 0.8% of the infused material was identified as 20-OH-LTB₄. LTB₄ was not excreted in the urine. Other nonvolatile metabolites of LTB₄ representing less than 0.4% each of the infused material were isolated from the urine. While there was an adequate quantity of some of these metabolites for partial characterization, there was insufficient material for structural elucidation. Further studies were performed in rabbits in which either LTB₄ or the structurally related compound 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE) were infused intravenously. In these rabbits the metabolism of LTB₄ and 8,15-diHETE was similar to that in the monkey with greater than 80% of the infused ³H-activity converted to tritiated water. These studies suggest that leukotriene B₄ and structurally related compounds undergo extensive degradation in vivo via the β-oxidation system.