title: Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation.
abstract: 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.
authors.affiliation: 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
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Pejman
authors.initials: P
authors.lastname: Dehghanyar
authors.forename: Bernd
authors.initials: B
authors.lastname: Seigfried
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Martin
authors.forename: Georg
authors.initials: G
authors.lastname: Menke
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
mesh_terms: 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
chemical_list: D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D013607:Tablets; D004008:Diclofenac