title: Randomized clinical comparisons of diclofenac concentration in the soft tissues and blood plasma between topical and oral applications.
abstract: OBJECTIVE
  To compare tissue concentrations of diclofenac resulting from topical and oral applications of diclofenac according to clinically recommended prescriptions.
  
  
  METHODS
  Diclofenac sodium was applied to 14 subjects (four male and 10 female), who were scheduled to undergo knee arthroplasty due to osteoarthritis, according to the oral or topical prescription (a capsule containing 37.5 mg diclofenac sodium or two tapes containing a total of 30 mg diclofenac sodium). At 12 h after prescription, the diclofenac concentration in the fat, muscle and synovial tissues was measured with liquid chromatography and mass analysis.
  
  
  RESULTS
  The diclofenac concentration in the muscle was significantly higher (P = 0.0196) after topical application (average 9.29 ng ml(-1)) than after oral application (0.66 ng ml(-1)), whereas there was no significant difference in the plasma diclofenac level (4.70 and 6.63 ng ml(-1)) between the two applications. The concentration in the synovial membrane was significantly (P = 0.0181) lower in the topical application (4.99 ng ml(-1)) than in the oral application (15.07 ng ml(-1)).
  
  
  CONCLUSIONS
  Whereas plasma levels resulting from topical and oral applications of diclofenac according to clinically recommended prescriptions were comparable, concentration levels in the muscle and synovial tissues were different.
authors.affiliation: Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Miyatake
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ichiyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Kondo
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yasuda
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019645:Arthroplasty, Replacement, Knee / Q000534:rehabilitation; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052097:Quadriceps Muscle / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac