Diclofenac concentrations in defined tissue layers after topical administration.
BACKGROUND
To date it is unclear whether therapeutic concentrations are attained in target tissues after topical administration of nonsteroidal anti-inflammatory drugs. Therefore this study in healthy volunteers was undertaken to measure diclofenac concentrations attained in defined tissue layers directly underlying the site of topical diclofenac application by in vivo microdialysis.


METHODS
In each experiment two microdialysis probes were inserted, one into a superficial (3.9 +/- 0.3 mm) and one into a deep (9.3 +/- 0.5 mm) tissue layer, in 20 healthy volunteers and calibrated in vivo. The distance between the surface of the skin and the tips of the microdialysis probes was measured by 7.5 MHz ultrasound. Diclofenac was administered topically as a single dose of approximately 300 mg/100 cm2. Concentration versus time profiles in tissue layers were monitored for 5 hours.


RESULTS
Concentration versus time profiles were obtained in 11 of 20 experiments. However, there was no correlation between area under the concentration-time curve (AUC) in a defined layer and the depth of probe insertion. In those experiments where concentration versus time profiles were obtained for both probes mean AUC was 532 +/- 197 microg x min x ml(-1) for superficial layers, and 438 +/- 249 microg x min x ml(-1) for deep layers.


CONCLUSIONS
We conclude that transdermal penetration of diclofenac, at least after single doses, is not predictable and may strongly be influenced by individual skin properties.
Müller
M
M
Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel, Austria.
Mascher
H
H
Kikuta
C
C
Schäfer
S
S
Brunner
M
M
Dorner
G
G
Eichler
H G
HG
D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis / Q000379:methods*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac