Application of the minimal trauma tissue biopsy to transdermal clinical pharmacokinetic studies

Although the transdermal administration of drugs has gained considerable im portance, reliable methods for the quantitative assessment of transdermal d rug penetration are scarce. The aim of the present study was therefore to e valuate the scopes and limits of the minimal trauma (issue biopsy (MTTB) te chnique for the in vivo characterization of the transdermal penetration pro cess and the assessment of dermal drug kinetics in humans following topical drug application. Nicotine TTS (21 mg/24 h) was administered transdermally to 13 healthy volunteers. Repeated minimally invasive dermal and subdermal tissue biopsies were obtained at defined time points from defined skin lay ers directly underlying the TTS. The position of the biopsy needle and dept h of biopsate were determined by 2D ultrasound scanning. The biopsy procedu re was well tolerated by all volunteers and up to six biopsies within a per iod of 10 h were easily accepted. Dermal pharmacokinetic profiles for nicot ine were obtained in all experiments and corresponded well to the values me asured in previous studies on transdermal nicotine penetration. Mean area u nder the nicotine concentration time curve (AUC) in subepidermal layers und erneath the application site of the TTS was 70.0 +/- 55.1 mug/g per h. Ther e was a correlation between the depth of biopsy sampling and dermal nicotin e concentrations at steady state (r=0.7). The MTTB is a suitable, well tole rated technique for the detection of transdermally applied compounds in def ined subepidermal tissue layers and could therefore become a valuable tool in the development and assessment of transdermal dosage forms. (C) 2001 Els evier Science B.V. All rights reserved.