Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation.
OBJECTIVE
The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets.


METHODS
Diclofenac (48 mg) was administered topically three times daily for 3 days onto a defined area of the thigh of 12 healthy males. After a 14-day wash out period, subjects were orally treated with 50 mg diclofenac three times daily for 3 days. In vivo microdialysis in subcutaneous and muscle tissues was performed immediately after the final doses from both treatments on day 4, and 48 h later. Plasma samples were taken simultaneously.


RESULTS
The relative bioavailability of diclofenac in subcutaneous adipose and skeletal muscle tissue was substantially higher after topical compared with oral dosing (324% and 209%, respectively) whereas relative plasma bioavailability was 50-fold lower. Plasma C(max) values were approximately 250-fold lower after topical compared with oral drug administration (i.e. median values = 4.89 ng mL(-1); 95% CI: 3.37-7.68 and 1240 ng mL(-1); 95% CI: 787-1389 ng mL(-1)). Both treatments were well tolerated.


CONCLUSIONS
Owing to its favourable penetration characteristics and low systemic availability, MIKA Diclofenac Spray Gel 4% is a rational alternative to oral diclofenac formulations for the treatment of inflammatory soft tissue conditions.
Brunner
Martin
M
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Allgemeines Krankenhaus-AKH, Waehringer-Guertel 18-20, A-1090 Vienna, Austria. martin.brunner@meduniwien.ac.at
Dehghanyar
Pejman
P
Seigfried
Bernd
B
Martin
Wolfgang
W
Menke
Georg
G
Müller
Markus
M
D000273:Adipose Tissue / Q000378:metabolism; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D004008:Diclofenac / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D005782:Gels; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D011446:Prospective Studies; D012869:Skin Absorption; D013607:Tablets
D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D013607:Tablets; D004008:Diclofenac