Benzoyl peroxide: percutaneous penetration and metabolic disposition. II. Effect of concentration.

The effect of drug concentrations of 2.5%, 5%, and 10% upon the transepidermal penetration of 14C-benzoyl peroxide in a lotion vehicle was assessed in excised human skin and in vivo in the rhesus monkey. In vitro, penetration of benzoyl peroxide was concentration-dependent, both as to rate and to amount, as measured by the hourly recovery of the metabolite, benzoic acid, from the dermal side of the model. In vivo, the higher the concentration of benzoyl peroxide applied, the greater the amount absorbed, as indicated by the urinary excretion of 14C-benzoic acid. Metabolic disposition of benzoyl peroxide, in turn, was unaffected by drug concentration. In all instances, the benzoyl peroxide absorbed was excreted rapidly in urine as benzoic acid; no hippuric acid was detected at any time. We conclude that (1) use of the excised human skin model for this compound can provide useful data in studies of the effects of vehicle and concentration on topical drug delivery, (2) the transepidermal delivery of benzoyl peroxide, but not its metabolic disposition, is concentration-dependent, and (3) the renal clearance of the systemically absorbed drug is so rapid that it precludes passage through the liver--therefore, no systemic toxicity due to drug accumulation can be expected.