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 10 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 nonmeasurable 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 14C were determined following a single 2.5 mg/kg intravenous administration of [14C]DMP.lactate. The concentrations of total 14C in all tissues were highest at 0.5 hr and declined with time thereafter. The highest concentration of 14C was in the kidneys, whereas the highest total amount was in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Bekersky
I
I
Department of Pharmacology and Toxicology, Fujisawa USA, Inc., Deerfield, IL 60015.
Puhl
R J
RJ
Hanson
G
G
Mong
S
S
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D000935:Antifungal Agents; D002250:Carbon Radioisotopes; C065259:1,3-di-(4-imidazolino-2-methoxyphenoxy)propane; D010419:Pentamidine