Kinetics of endogenous leukotriene B sub(4) and E sub(4) production following injection of the chemotactic peptide FMLP in the rabbit

• Published in: Prostaglandins Vol. 54; no. 4; pp. 699 - 712
• Main Authors: Celardo, A, Dell'Elba, G, Manarini, S, Evangelista, V, de Gaetano, G, Cerletti, C
• Format: Journal Article
• Language: English
• Published: 01-10-1997
• ISSN: 0090-6980

The kinetic profiles of leukotriene B sub(4) (LTB sub(4)) and E sub(4) (LTE sub(4)) after intravenous administration (30 nmol/kg) of the inflammatory peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) were evaluated in male rabbits. LTB sub(4) and LTE sub(4) reached the maximal concentration of 84.2 plus or minus 60.0 and 162.2 plus or minus 51.4 nmol/L (mean plus or minus s.d.), at 2 and 5 min, respectively. The first elimination phase for LTB sub(4) and LTE sub(4), after FMLP administration, showed an apparent half-life of 24.6 plus or minus 6.7 and 36.9 plus or minus 13.0 min, respectively. The area under the blood concentration-time curve (AUC, nmol min/L) of LTB sub(4) and LTE sub(4) was 2178 plus or minus 1591 and 7627 plus or minus 3052, respectively. LTE sub(4) and N-ac-LTE sub(4) 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-LTE sub(4) 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.