KINETICS OF ENDOGENOUS LEUKOTRIENE B-4 AND E-4 PRODUCTION FOLLOWING INJECTION OF THE CHEMOTACTIC PEPTIDE FMLP IN THE RABBIT

The kinetic profiles of leukotriene B-4 (LTB4) and E-4 (LTE4) after in travenous administration (30 nmol/kg) of the inflammatory peptide N-fo rmyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were evaluated in mal e 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, respe ctively. The first elimination phase for LTB4 and LTE4, after FMLP adm inistration, showed an apparent half-life of 24.6 +/- 6.7 and 36.9 +/- 13.0 min, respectively. The area under the blood concentration-time c urve (AUC, nmol min/L) of LTB4 and LTE4 was 2178 +/- 1591 and 7627 +/- 3052, respectively. LTE4 and N-ac-LTE4 were the major components excr eted in the urine, mostly in the first time interval (0-12 h) of urina ry 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 leu kotrienes 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.