Metabolism of leukotriene C4 in the anesthetized guinea pig

The distribution and metabolism of [3H] leukotriene (LT)C4 has been studied in the anesthetized guinea pig. The intravenous administration of [3H] LTC4 (1 muCi/kg) to seven guinea pigs showed a rapid vascular clearance of radioactivity with significant metabolism evident at the 15 sec and 1 min time points with material chromatographing like LTC4 (45.6 +/- 7.5%, 35.0 +/- 4.4%). LTD4 (18.4 +/- 5.1%, 33.2 +/- 4.4%) as well as polar material (25.5 +/- 6.0%, 29.7 +/- 4.7%) respectively. The biliary recovery of radioactivity was found to be 74.5 +/- 5.5% n = 4, over 120 min in the guinea pig with less than 1% of radioactivity present in the urine. Examination of the metabolic profile of the biliary radioactivity showed total conversion of LTC4 to LTD4 which was the major metabolite at early time points, and LTD4 as well as LTE4 at later time points. Significant radioactivity which increased with time was also present at the solvent front of the chromatogram indicating the presence of polar biliary metabolites. These results show that the major route of elimination of peptide leukotrienes is through the bile duct in the anesthetized guinea pig and that LTD4 is the major eliminated metabolite in this model.