TRANSCUTANEOUS CHEMICAL COLLECTION OF CAFFEINE IN NORMAL SUBJECTS - RELATIONSHIP TO AREA UNDER THE PLASMA CONCENTRATION-TIME CURVE AND SWEAT PRODUCTION

A novel transcutaneous chemical collection device (TCD) has been developed to study the phenomenon of outward transcutaneous chemical migration. The TCD is a Bandaid-like device containing an immobilized aqueous media and binding reservoir material to prevent back-transfer into the skin. This device, when placed against the skin, allows collection and quantitation of chemicals that diffuse directly through the skin from within the body. The relationship of the amount of drug collected in the TCD to the amount in the body available for collection (as represented by the area under the plasma-concentration time curve, AUC) and the effects of sweating, a potential confounding factor, on collection of drug in a TCD were studied, using caffeine as a model compound. TCD were placed on the skin of normal male volunteers. Twenty-four hours later subjects took caffeine by mouth. Blood samples were collected and TCD were removed at various times after drug intake and analyzed by HPLC for caffeine. Studies of the sweating effect were carried out in a similar manner, except that one arm of each subject was maintained at 40-degrees-C to induce local sweating, the other arm acted as a non-sweating control. The amount of caffeine collected was linearly related to the AUC. Sweating seemed to have a large (40%) contribution to transdermal collection in the early period (5.5 h) of the study, but this difference was much less (14%) at longer collection times (10 h).