Kinetics of Endogenous Leukotriene B4 and E4 Production Following Injection of the Chemotactic Peptide FMLP in the Rabbit

Abstract

The kinetic profiles of leukotriene B₄ (LTB₄) and E₄ (LTE₄) after intravenous administration (30 nmol/kg) of the inflammatory peptide N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) were evaluated in male rabbits. LTB₄ and LTE₄ reached the maximal concentration of 84.2 ± 60.0 and 162.2 ± 51.4 nmol/L (mean ± s.d.), at 2 and 5 min, respectively. The first elimination phase for LTB₄ and LTE₄, after FMLP administration, showed an apparent half-life of 24.6 ± 6.7 and 36.9 ± 13.0 min, respectively. The area under the blood concentration-time curve (AUC, nmol min/L) of LTB₄ and LTE₄ was 2178 ± 1591 and 7627 ± 3052, respectively. LTE₄ and N-ac-LTE₄ were the major components excreted in the urine, mostly in the first time interval (0–12 h) of urinary collection after FMLP treatment; 11-trans-LTE₄ was recovered in the second interval (12–24 h). Two other more polar compounds, potential metabolites, were recovered in the first interval of urine collection. Knowledge of the kinetic characteristics of endogenously produced leukotrienes may be useful in understanding the role of these eicosanoids in inflammatory and thrombotic disease, as well as in evaluating the efficacy of drugs designed to modulate their production and effect.