title: Diclofenac systemic bioavailability of a topical 1% diclofenac + 3% menthol combination gel vs. an oral diclofenac tablet in healthy volunteers: a randomized, open-label, crossover study .
abstract: OBJECTIVE
  Evaluate systemic exposure with repeated topical application of a fixed-combination topical gel product containing 1% diclofenac sodium and 3% menthol in either of 2 formulation packages relative to oral administration.
  
  
  METHODS
  In this phase 1, single-center, 4-way crossover study, healthy volunteers aged 18 - 50 years underwent consecutive 3-day treatment regimens in a randomly assigned sequence with each of 4 treatment groups: 4 g of topical 1% diclofenac + 3% menthol gel administered via an aluminum tube or roll-on device applied 4 times daily; 4 g of topical 1% diclofenac sodium gel (Voltaren Gel) applied 4 times daily; and oral diclofenac sodium tablets 50 mg 3 times daily. Treatment regimens were separated by 2-day washout periods.
  
  
  RESULTS
  A total of 18 subjects enrolled and completed the study. Relative to oral administration, area under the concentration time curve from 48 to 72 hours (AUC48-72) with topical administration of 1% diclofenac + 3% menthol gel from a tube or roll-on device was 16.1% (90% CI: 12.2 - 21.1%) and 14.4% (90% CI: 11.0 - 19.0%), respectively. The diclofenac/menthol combination delivered significantly higher exposures of diclofenac compared with Voltaren Gel. A higher number of adverse events (AEs) occurred with the topical diclofenac/menthol combination (61%) vs. Voltaren Gel (22%) or oral diclofenac (6%); most were local skin reactions. No difference in systemic AEs was observed among the groups.
  
  
  CONCLUSIONS
  As expected, systemic exposure was significantly lower with the topical diclofenac/menthol treatment regimens compared with oral diclofenac. Local skin AEs were increased with the topical combination product, but the risk of systemic AEs was low. .
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Moreira
authors.forename: D Jeffery
authors.initials: DJ
authors.lastname: Liu
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005782:Gels; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008610:Menthol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009518:New York; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D005782:Gels; D013607:Tablets; D004008:Diclofenac; D008610:Menthol