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% dextr ose) solution. Following the intravenous administration, plasma concen trations of DMP declined in an apparent biexponential manner and were nonmeasurable after 24 hr. The mean terminal plasma elimination half-l ife 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. T he 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 t he 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 administra tion, respectively. The tissue distribution and mass balance of total C-14 were determined following a single 2.5 mg/kg intravenous administ ration of [C-14]DMP-lactate. The concentrations of total C-14 in all t issues were highest at 0.5 hr and declined with time thereafter. The h ighest concentration of C-14 was in the kidneys, whereas the highest t otal amount was in the liver. Decline of C-14 from kidneys and liver w as apparently biexponential, whereas it was monoexponential from the l ungs. The concentrations and amounts of radioactivity in all other tis sues 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 su bstantial fecal excretion following intravenous administration suggest s that the in vivo disposition of DMP in rats includes biliary excreti on.