Metabolism of a New Bactericidal Antiseptic, OPB-2045, in Rats following Subcutaneous Administration.

Abstract

To investigate the metabolism and disposition of OPB-2045, 1-(3, 4-dichlorobenzyl)-5-octylbiguanide, 14C-labeled OPB-2045 was subcutaneously injected to male Sprague-Dawley rats at a dose of 1 mg/kg and the resulting radioactivity in the urine and bile was analyzed using a high-performance liquid radiochromatography. The radioactivity retained at the injection site was also analyzed. 1. The metabolites excreted in the urine included 6-[5-(3, 4-dichlorobenzyl)-1-biguanidino] hexanoic acid (DM-210), 4-[5-(3, 4-dichlorobenzyl)-1-biguanidino] butanoic acid (DM-212), 5-[5-(3, 4-dichlorobenzyl)-1-biguanidino] pentanoic acid (DM-213) and 3, 4-dichlorobenzoic acid. Within 72 hr after the dosing, the metabolites DM-210, DM-212, DM-213, and 3, 4-dichlorobenzoic acid excreted in the urine accounted for 4.6, 1.6, 1.5 and 1.4% of the administered dose, respectively. No excretion of the unchanged compound was detected in the urine. 2. The metabolites excreted in the bile included DM-210, DM-212 and DM-213. The combined excretion rate of these metabolites accounted for 15.6% of the dose within 24 hr postdosing. No excretion of 3, 4-dichlorobenzoic acid or the unchanged OPB-2045 was detected in the bile. 3. The radioactivity retained at the injection site at 1, 8 and 24 hr postdosing accounted for 51.5%, 34.6% and 13.0% of the administered dose, respectively. The unchanged compound was found to account for at least 80.8% of the radioactivity, and no metabolites including DM-210, DM-212, DM-213 and 3, 4-dichlorobenzoic acid, were detected. These results indicated that OPB-2045 was not metabolized by the skin/tissues at the injection site, but instead by other organ(s).