PMID- 27936526
OWN - NLM
STAT- MEDLINE
DCOM- 20170619
LR  - 20221222
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 55
IP  - 4
DP  - 2017 Apr
TI  - 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
.
PG  - 368-372
LID - 10.5414/CP202753 [doi]
AB  - 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 (AUC(48-72)) 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. CONCLUSION: 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.
.
FAU - Moreira, Sebastian A
AU  - Moreira SA
FAU - Liu, D Jeffery
AU  - Liu DJ
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 0 (Analgesics)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Drug Combinations)
RN  - 0 (Gels)
RN  - 0 (Tablets)
RN  - 144O8QL0L1 (Diclofenac)
RN  - 1490-04-6 (Menthol)
SB  - IM
MH  - Administration, Cutaneous
MH  - Administration, Oral
MH  - Adult
MH  - Analgesics/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Diclofenac/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Drug Combinations
MH  - Female
MH  - Gels
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Menthol/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - New York
MH  - Tablets
MH  - Therapeutic Equivalency
MH  - Young Adult
EDAT- 2016/12/13 06:00
MHDA- 2017/06/20 06:00
CRDT- 2016/12/13 06:00
PHST- 2017/04/07 00:00 [accepted]
PHST- 2016/12/13 06:00 [pubmed]
PHST- 2017/06/20 06:00 [medline]
PHST- 2016/12/13 06:00 [entrez]
AID - 14985 [pii]
AID - 10.5414/CP202753 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2017 Apr;55(4):368-372. doi: 10.5414/CP202753.