Co-Authors:
Ezra, D., Departments of Pharmacology and Medical Chemistry Merck Frosst Canada Inc. P.O. Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada
Foster, A., Departments of Pharmacology and Medical Chemistry Merck Frosst Canada Inc. P.O. Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada
Cirino, M., Departments of Pharmacology and Medical Chemistry Merck Frosst Canada Inc. P.O. Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada
Rokach, J., Departments of Pharmacology and Medical Chemistry Merck Frosst Canada Inc. P.O. Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada
Letts, L.G., Departments of Pharmacology and Medical Chemistry Merck Frosst Canada Inc. P.O. Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada
Abstract:
The metabolism of leukotriene (LT)C4 and its major routes of elimination in vivo have been studied in four anesthetized domestic pigs administered intravenous [3H]-LTC4 (0.5 μCi/kg). The kinetic profile of LTC4 in the blood was followed for 60 min after administration while the biliary and urinary excretion of LTC4 and its metabolites were determined over a 120 min interval. The total recovery of radioactivity in bile and urine was 45% ± 1 (n = 3) and 18% (n = 2) respectively. Examination of the radioactive metabolites in bile showed LTD4 (44% of biliary content) and LTE4 (21% of biliary content) as the major identified lipoxygenase products at t 1 2 (27 min). The only identified cysteinyl leukotriene observed in the urine was LTE4 (13% of urinary content). In both bile and urine substantial amount of radioactivity were detected at the solvent front of the reverse phase chromatographic system indicating the presence of additional unidentified metabolites. We suggest that measurement of metabolites using these sampling methods may be useful for the detection and measurement of peptide leukotriene production in vivo. © 1987.
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