Preliminary results on the total radioactivity distribution upon parenteral administration of 14C-coumarin to DBA/2 mice.

The time related distribution patterns of coumarin (C) and its main metabolite 7-hydroxycoumarin (7-HC) were studied in DBA/2/lac mice following retroorbital injection of 14C-labelled C. The total radioactivity was determined as counts per minute per ml or g wet weight over a period of 60 min. In blood, brain, heart, lung, muscle and spleen peak concentrations were observed 2.5 min after dosing. The liver and kidney showed the greatest accumulation with peak concentrations being reached after 10 min. Blood and brain concentrations were equal. Unmetabolized C was found in all organs studied; 7-HC was found in all organs but brain, and the glucuronide of 7-HC was found in all organs but brain and spleen. Apparently C crosses the blood brain barrier but the metabolites do not. The decay of the total radioactivity versus time appears to be best fitted to a two-compartment model for brain, heart, lung, muscle, and spleen, and to a one-compartment model for blood, liver and kidney. The terminal half-life in blood was 0.24 h.