Yeung D, Nacht S, Bucks D, Maibach H I
J Am Acad Dermatol. 1983 Dec;9(6):920-4. doi: 10.1016/s0190-9622(83)70209-4.
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.
评估了2.5%、5%和10%的药物浓度对含14C - 过氧化苯甲酰洗剂经皮渗透的影响，研究在切除的人体皮肤和恒河猴体内进行。在体外，以模型真皮侧代谢物苯甲酸的每小时回收率衡量，过氧化苯甲酰的渗透在速率和量上均呈浓度依赖性。在体内，如14C - 苯甲酸的尿排泄所示，过氧化苯甲酰应用浓度越高，吸收量越大。反过来，过氧化苯甲酰的代谢处置不受药物浓度影响。在所有情况下，吸收的过氧化苯甲酰均迅速以苯甲酸形式经尿液排泄；任何时候均未检测到马尿酸。我们得出结论：(1) 对于该化合物，使用切除的人体皮肤模型可在载体和浓度对局部给药影响的研究中提供有用数据；(2) 过氧化苯甲酰的经皮递送呈浓度依赖性，但其代谢处置并非如此；(3) 全身吸收药物的肾清除非常迅速，以至于排除了其通过肝脏的可能性——因此，预计不会因药物蓄积产生全身毒性。
