Transdermal penetration of diclofenac after multiple epicutaneous administration.
OBJECTIVE
To test whether therapeutic diclofenac concentrations are attained in skeletal muscle tissue beneath the application site of an epicutaneously administered diclofenac foam formulation.


METHODS
Diclofenac foam (5%) was administered epicutaneously at the thigh 80 mg/200 cm2 twice daily for a period of 7 days in healthy volunteers (n=12). On Day 8, 2 microdialysis probes were inserted into skeletal muscle tissue beneath the application site and an 80 mg dose was administered epicutaneously. Concentration versus time profiles in plasma and skeletal muscle were followed for 10 hours.


RESULTS
Concentration versus time profiles were obtained for plasma and interstitial muscle fluid in all experiments. Mean Cmax in plasma was 18.75+/-4.97 ng/ml. Corresponding interstitial concentrations in skeletal muscle were significantly higher, 219.68+/-66.36 ng/ml (p=0.01). Plasma concentrations were not correlated to tissue concentrations (r=-0.08).


CONCLUSIONS
There is significant direct penetration of diclofenac into skeletal muscle following multiple epicutaneous administration. However, the concentration attained in individual subjects is not predictable and may be strongly influenced by individual skin properties.
Müller
M
M
Department of Clinical Pharmacology, University of Vienna, Austria. markus.mueller@univie.ac.at
Rastelli
C
C
Ferri
P
P
Jansen
B
B
Breiteneder
H
H
Eichler
H G
HG
D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D012869:Skin Absorption
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac