Intradermal microdialysis: Kinetics of iontophoretically delivered propranolol in forearm dermis

Intradermal microdialysis permits us to measure the concentration in dermis of drugs applied to the skin. Microdialysis is especially efficient in sam pling water-soluble molecules. Consequently, it appears particularly suitab le to study current based delivery systems like iontophoresis that deliver ions or highly polar molecules. The purpose of this work was to evaluate th e adequacy of a skin microdialysis technique to characterize and quantify t he dermatopharmacokinetics of iontophoretically delivered propranolol in th e dermis of healthy human volunteers. Linear microdialysis probes were inse rted in the subject's forearm skin and an iontophoresis device was installe d above them. Constant current was applied for two periods of 1 h each sepa rated by a 1-h interval. Dialysate samples were collected every 6 min for 4 .4 h and analyzed by HPLC. Probes were always placed in the dermis as measu red by ultrasonography. Propranolol was detectable in the dialysate. It was possible to build detailed concentration vs. midtime profiles that mirrore d the current applied. Elimination rate from the dermis had first-order kin etics and was similar in all subjects. Quantification of the absorption pro cess, indexed by lag-time and area under the concentration curve showed a h igh inter- and intrasubject variability that did not correlate with probe d epth. (C) 2000 Elsevier Science B.V. All rights reserved.