Percutaneous Absorption and Tissue Distribution of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045) in Rats.

Abstract

The absorption and tissue distribution of OPB-2045, a new antiseptic antimicrobial drug with a biguanide moiety in the molecule, were studied in male Sprague-Dawley rats with intact or damaged skin following a single and repetitive dermal application of 0.1% 14C-OPB-2045 in a liquid formulation applied at the dose of 0.3 mg/rat to 6.25 cm2 of the skin. Comparative percutaneous absorption was also investigated in rats treated with single doses of 0.04% 14C-OPB-2045 and 14C-chlorhexidine in aqueous solution at 0.12 mg/rat to the same area of the skin. Radioactivity was hardly detected in the serum of rats with intact and damaged skin during a 24-hr period after single topical application of 0.1% 14C-OPB-2045. Urinary and fecal excretions of radioactivity within 336 hr after single dosing were 1.20/ and 4.1% of the dose, respectively, in rats with intact skin, and 2.4% and 5.0%, respectively, in rats with damaged skin, indicating no significant differences. Percutaneous absorption was estimated to be approximately 1.40/ of the total dose in rats with intact skin following repetitive dermal application of the compound. Radioactivity in various tissues was quite low except the application site of the compound, and the disappearance of radioactivity from the application site was sluggish in intact and damaged skin rats. Percutaneous absorption of 14C-OPB-2045 and 14C-chlorhexidine in aqueous solution was 4.20/ and 4.2% of the dose respectively in intact skin, and 7.1% and 3.8% respectively in damaged skin. The percutaneous absorption of OPB-2045 is thus quite poor, and essentially the same to chlorhexidine. Stratum corneum, an important tissue as a barrier controlling percutaneous absorption of chemicals does not appear to be important to the absorption of either OPB-2045 or chlorhexidine through the skin.