PERCUTANEOUS-ABSORPTION OF AZONE FOLLOWING SINGLE AND MULTIPLE DOSES TO HUMAN VOLUNTEERS

Azone (1-dodecylazacycloheptan-2-one) is an agent that has been shown to enhance percutaneous absorption of drugs. Azone is thought to act b y partitioning into skin lipid bilayers and thereby disrupting the str ucture. An open-label study was done with nine volunteers (two males, seven females; aged 51-76 years) in which Azone cream (1.6%; 100 mg) w as topically dosed on a 5 X 10-cm area of the ventral forearm for 21 c onsecutive days. On days 1, 8, and 15, the Azone cream contained 47 mu Ci of [C-14]Azone. The skin application site was washed with soap and water after each 24-h dosing. Percutaneous absorption was determined by urinary radioactivity excretion. The [C-14]Azone was ring labeled [ C-14-2-cycloheptan]. Radiochemical purity was >98.6% and cold Azone pu rity was 99%. Percutaneous absorption of the first dose (day 1) was 1. 84 +/- 1.56% (SD) of applied dose for 24-h skin application time. Day 8 percutaneous absorption, after repeated application, increased signi ficantly (p < 0.002) to 2.76 +/- 1.91%. Day 15 percutaneous absorption , after continued repeated application, stayed the same at 2.72 +/- 1. 21%. In humans, repeated application of Azone results in an initial se lf-absorption enhancement, probably due to its mechanism of action. Ho wever, steady-state percutaneous absorption of Azone is established af ter this initial change. Thus, Azone can enhance its own absorption as well as that of other compounds. This should be considered relevant f or any pharmalogical or toxicological evaluation. Washing the skin sit e of application with soap and water only recovered 1-2% of applied ra dioactivity. Previous published studies recovered the Azone dose with ethanol washes. Thus, there could potentially be an accumulation of Az one in skin.