title: Study of the percutaneous penetration of flurbiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat.
abstract: The percutaneous penetration of flurbiprofen delivered by iontophoresis was investigated in the hairless rat. Unbound concentrations of flurbiprofen in dermis and subcutaneous tissue were continuously measured by on-line microdialysis. Simultaneously, a conventional blood sampling was performed. Linear microdialysis probes were implanted in dermis and in subcutaneous tissue at a depth of 398.3 +/- 15.3 and 1878 +/- 35.8 microm, respectively. Commercial patches were used to deliver flurbiprofen for 15 min at a current density of 0.4 mA/cm(2). In vivo recoveries of both probes, determined by using naproxen as retrodialysis calibrator, were 26.0 +/- 0.3 and 72.9 +/- 0.7% for dermal and subcutaneous probe, respectively. After iontophoretic delivery, a gradient in mean tissue unbound concentrations was observed, with a C(max) in dermis of 8.7 +/- 0.4 microg/mL as compared with subcutaneous C(max) of 0.5 +/- 0.1 microg/mL. The area under the unbound concentration curve in dermis was 13-fold higher than that in the subcutaneous tissue. Total plasma concentration curves showed a rapid absorption phase with a T(max) of 30 min and C(max) of 1.8 +/- 0.1 microg/mL. In conclusion, iontophoresis delivery was demonstrated to be efficient to deliver a high amount of flurbiprofen in dermis and underlying tissue with a fast input rate whereas maintaining a low plasma exposure.
authors.affiliation: Unité de Pharmacie Galénique, Industrielle et Officinale, Université catholique de Louvain, Avenue E. Mounier 73, UCL 73.20, 1200 Brussels Belgium.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mathy
authors.forename: Catherine
authors.initials: C
authors.lastname: Lombry
authors.forename: Roger K
authors.initials: RK
authors.lastname: Verbeeck
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000287:Administration, Topical; D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005480:Flurbiprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D007202:Indicators and Reagents; D007478:Iontophoresis; D008297:Male; D017551:Microdialysis; D051381:Rats; D012869:Skin Absorption
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D005480:Flurbiprofen