Yucatan micropig皮膚を介したin vitro透過性からニコチンテープまたはリドカインテープをヒトに適用後の血中濃度の予測

抄録

The purpose of this study was to estimate whether the in vitro permeation parameters through Yucatan micropig (YMP) skin can be used to predict blood concentration profiles of drugs after topical application of transdermal therapeutic systems (TTS) in humans. In vitro permeation studies were performed after application of Nicotinell^® TTS^® 20 (Nicotine Tape) or Penles^® Tape 18 mg (Lidocaine Tape) on the excised dermis-split (split) or stratum corneum-stripped and dermis-split (stripped/split) YMP skin using vertical diffusion cells. Diffusion coefficients and partition coefficients of nicotine or lidocaine through the YMP skin were calculated using analysis software for TTS, SKIN-CAD^®. Pharmacokinetic parameters of nicotine or lidocaine after intravenous infusion in human, YMP skin thickness, YMP and human stratum corneum thickness, and distance from the human skin surface to capillary vessel were used as input parameters into SKIN-CAD^® to calculate blood concentration profiles of nicotine or lidocaine after topical application of Nicotine Tape or Lidocaine Tape, respectively, in human. The predicted profiles of blood concentration (C_max, t_max and AUC) of nicotine or lidocaine were well consistent with the observed profiles (literature values). The ratios of predicted blood concentration to observed one for nicotine or lidocaine were from 0.7 to 1.2. Thus, blood concentration after topical application of TTS in human could be precisely predicted from the in vitro split (0.4 mm) YMP skin permeation parameters. These results suggest that the in vitro permeation experiments using split (0.4 mm) YMP skin is useful for predicting blood concentration profiles after topical application of drugs in humans.