Metabolism and biliary excretion of phenanthridinium salts—II

The biliary excretion of phenanthridinium salts has been investigated in rats with ligated renal pedicles. The biliary excretion of the four phenanthridinium compounds investigated took place against large bile-blood concentration gradients and became constant with increasing dose. 150C47 (3, 8-diamino-6- p -aminophenyl-5-methylphenanthridinium chloride) was investigated in detail to determine if it is excreted into bile by the specific metabolically dependent transport system that has been proposed for a number of other quaternary ammonium compounds, including certain phenanthridinium compounds. The excretion of total diazotizable material in bile reached a maximum at a dose of about 20 mg/kg and then remained constant as the dose was increased further. This maximum was not a result of either decreased bile flow or a limited ability of the liver to accumulate 150C47. The excretion of free 150C47 increased with dose over the entire dose range investigated (0–50 mg/kg), whereas its monoacetyl metabolite reached a maximum rate of excretion at 15–20 mg/kg and then decreased as the dose was increased further. The excretion of both forms was directly proportional to dehydrocholate-induced bile flow, but independent of the decrease in flow caused by the intravenous administration of hypertonic sucrose. The possible role of bile salts in the excretion of phenanthridinium compounds is discussed, and data in vitro on the binding of 150C47 to plasma proteins and liver homogenates and its complexing with bile are presented in connection with this point. The behavior of this compound is compared with that of procaineamide ethobromide, a quaternary compound for which a specific metabolically dependent transport system has been proposed.