DISPOSITION OF A NEW ANTIINFECTIVE AGENT 1,3-DI(4-IMIDAZOLINO-2-METHOXYPHENOXY)PROPANE IN MALE-RATS

The disposition of 1,3-di[4-imidazolino-2-methoxyphenoxy]propane (DMP) is described in male rats following a single 2.5 mg/kg intravenous or 16 mg/kg oral administration of DMP . lactate in an aqueous (5% dextrose) solution. Following the intravenous administration, plasma concentrations of DMP declined in an apparent biexponential manner and were nonmeasurable after 24 hr. The mean terminal plasma elimination half-life was 14.9 hr. A volume of distribution of 18.7 liters/kg and a body clearance of 14.5 ml/min/kg were estimated. After oral administration, mean plasma concentrations of DMP reached a maximum of 39.6 ng/ml at 15 min and were non-measurable after 4 hr. The areas under the curve (AUC)0-24 of DMP was 2276 ng . hr/ml following the intravenous dose. The AUC0-4 was 68 ng . hr/ml following the oral dose. The AUC0-4 was 68 ng - hr/ml following the oral dose. Based on a comparison of AUC0-4 the oral bioavailability was 0.9%. A mean of 41.7 and 0.4% of the dose was excreted in urine as DMP following intravenous and oral administration, respectively. The tissue distribution and mass balance of total C-14 were determined following a single 2.5 mg/kg intravenous administration of [C-14]DMP-lactate. The concentrations of total C-14 in all tissues were highest at 0.5 hr and declined with time thereafter. The highest concentration of C-14 was in the kidneys, whereas the highest total amount was in the liver. Decline of C-14 from kidneys and liver was apparently biexponential, whereas it was monoexponential from the lungs. The concentrations and amounts of radioactivity in all other tissues were small by comparison. The combined total amount represented <0.5% of the dose at any given time point. A total of 73.4% of the C-14 dose was excreted in urine (45.7%) and feces (23.2%) in 72 hr. The substantial fecal excretion following intravenous administration suggests that the in vivo disposition of DMP in rats includes biliary excretion.