Determination of the in vivo bioavailability of iontophoretically delivered diclofenac using a methyl nicotinate skin inflammation assay.
OBJECTIVE
In this study, we investigated the bioavailability of iontophoretically delivered diclofenac with the methylnicotinate (MN) test. The inhibition of an erythema provoked by MN is proportional to the bioavailability of diclofenac in the skin. It was our aim to use this procedure in the determination of the contribution of, respectively, passive diffusion, occlusion and electrically assisted delivery during an iontophoretic procedure as used in physiotherapy.


METHODS
A total of six application sites were marked on the volar forearms of each volunteer (n=12), for the following treatment and/or control modes: A=cathodal iontophoresis of 12 mg/cm(2) Voltaren Emulgel (diethylammonii diclofenac 1%) for 20 min; B=passive diffusion under a contact sponge; C=passive diffusion without any covering; D=current alone; E=standard MN response; and F=blanco site. Tristimulus surface colorimetry and Laser Doppler flowmetry were used to measure, respectively, the skin color and the perfusion of the microcirculation. Bioavailability was assessed by quantification of an MN-induced erythema under the different conditions.


RESULTS
A significant reduction of the MN-induced erythema was observed with the Chromameter and Laser Doppler measurements for the following treatment modalities: (1) electrically assisted delivery: respectively, 65% and 100%, (2) application under a contact sponge: 66% and 97% and (3) passive diffusion without any covering: 32% and 65%. A significant reduction was equally observed for the site treated with the current alone: 19% and 42%. There was no significant difference between the response after iontophoretic-delivered diclofenac (mode A) and application of diclofenac under a contact sponge (mode B).


CONCLUSIONS
The procedure used enabled us to evaluate the bioavailability of a non-steroidal anti-inflammatory drug in the skin. Under the conditions used, we did not find an increased bioavailability after electrically assisted delivery of diclofenac compared with the passive percutaneous penetration under the contact sponge.
Lambrecht
Renzo
R
Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, BIOM, Plainlaan 2, 1050 Brussels, Belgium.
Clarys
Peter
P
Clijsen
Ron
R
Barel
André O
AO
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D007478:Iontophoresis / Q000379:methods; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D015999:Multivariate Analysis; D009539:Nicotinic Acids / Q000009:adverse effects*; D012867:Skin / Q000098:blood supply
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009539:Nicotinic Acids; D004008:Diclofenac; C008473:methyl nicotinate