Effects of vehicle on the uptake and elimination kinetics of capsaicinoids in human skin in vivo.

While the physiologic and molecular effects of capsaicinoids have been extensively studied in various model systems by a variety of administration routes, little is known about the uptake and elimination kinetic profiles in human skin following topical exposure. The present study evaluated the uptake and elimination kinetics of capsaicinoids in human stratum corneum following a single topical exposure to 3% solutions containing 55% capsaicin, 35% dihydrocapsaicin, and 10% other analogues prepared in three vehicles: mineral oil (MO), propylene glycol (PG), and isopropyl alcohol (IPA). Capsaicinoid solutions were evaluated simultaneously in a random application pattern on the volar forearms of 12 subjects using a small, single 150-microg dose. Capsaicin and dihydrocapsaicin were recovered from human skin using commercial adhesive discs to harvest stratum corneum from treated sites. Capsaicinoids were extracted from the stratum corneum-adhesive discs and quantified by liquid chromatography/mass spectroscopy (LC/MS). Both capsaicinoids were detected in stratum corneum 1 min after application with all vehicles and achieved a pseudo-steady state shortly thereafter. IPA delivered three times greater capsaicin and dihydrocapsaicin into the human stratum corneum than PG or MO at all time points investigated. The Cmax of capsaicin in IPA, PG, and MO was 16.1, 6.2, and 6.5 microg, respectively. The dihydrocapsaicin content was 60% of capsaicin with all vehicles. The estimated T(half) of capsaicin and dihydrocapsaicin in the three vehicles was similar (24 h). Thus, maximal cutaneous capsaicinoid concentrations were achieved quickly in the human stratum corneum and were concentration and vehicle dependent. In contrast, capsaicinoid half-life was long and vehicle independent.