1: J Pharm Sci. 2005 Jan;94(1):144-52. 

Study of the percutaneous penetration of flurbiprofen by cutaneous and
subcutaneous microdialysis after iontophoretic delivery in rat.

Mathy FX, Lombry C, Verbeeck RK, Preat V.

Unite de Pharmacie Galenique, Industrielle et Officinale, Universite catholique
de Louvain, Avenue E. Mounier 73, UCL 73.20, 1200 Brussels Belgium.

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. (c)
2004 Wiley-Liss, Inc.

PMID: 15761938 [PubMed - in process]