Penetration of topical diclofenac into synovial tissue and fluid of osteoarthritic knees: a multicenter, randomized, placebo-controlled, pharmacokinetic study.
diclofenac
nonsteroidal anti-inflammatory agents
osteoarthritis
pharmacokinetics; tissue distribution
Journal
Therapeutic advances in musculoskeletal disease
ISSN: 1759-720X
Titre abrégé: Ther Adv Musculoskelet Dis
Pays: England
ID NLM: 101517322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
12
05
2020
accepted:
25
06
2020
entrez:
14
9
2020
pubmed:
15
9
2020
medline:
15
9
2020
Statut:
epublish
Résumé
Topical diclofenac, a nonsteroidal anti-inflammatory drug, has proven efficacy and safety in the management of osteoarthritis pain. We investigated penetration of topical diclofenac into knee synovial tissue and fluid (primary objective) and evaluated relative exposure in the knee In this phase I, double-blind, multicenter study, patients scheduled for arthroplasty for end-stage knee osteoarthritis were randomly assigned 2:1 to 4 g diclofenac diethylamine 2.32% w/w gel (92.8 mg diclofenac diethylamine, equivalent to 74.4 mg diclofenac, per application) or placebo gel, applied to the affected knee by a trained nurse/designee every 12 h for 7 days before surgery. Diclofenac concentrations were measured in synovial tissue, synovial fluid and plasma from samples obtained during surgery ⩾12 h after last application. Treatment-emergent adverse events (TEAEs) were evaluated. Evaluable synovial tissue or fluid samples were obtained from 45 (diclofenac Topical diclofenac diethylamine 2.32% w/w gel penetrated into the osteoarthritic knee after repeated application and remained detectable in synovial tissue and fluid at the end of the final 12 h dosing cycle.
Sections du résumé
BACKGROUND
BACKGROUND
Topical diclofenac, a nonsteroidal anti-inflammatory drug, has proven efficacy and safety in the management of osteoarthritis pain. We investigated penetration of topical diclofenac into knee synovial tissue and fluid (primary objective) and evaluated relative exposure in the knee
METHODS
METHODS
In this phase I, double-blind, multicenter study, patients scheduled for arthroplasty for end-stage knee osteoarthritis were randomly assigned 2:1 to 4 g diclofenac diethylamine 2.32% w/w gel (92.8 mg diclofenac diethylamine, equivalent to 74.4 mg diclofenac, per application) or placebo gel, applied to the affected knee by a trained nurse/designee every 12 h for 7 days before surgery. Diclofenac concentrations were measured in synovial tissue, synovial fluid and plasma from samples obtained during surgery ⩾12 h after last application. Treatment-emergent adverse events (TEAEs) were evaluated.
RESULTS
RESULTS
Evaluable synovial tissue or fluid samples were obtained from 45 (diclofenac
CONCLUSIONS
CONCLUSIONS
Topical diclofenac diethylamine 2.32% w/w gel penetrated into the osteoarthritic knee after repeated application and remained detectable in synovial tissue and fluid at the end of the final 12 h dosing cycle.
Identifiants
pubmed: 32922524
doi: 10.1177/1759720X20943088
pii: 10.1177_1759720X20943088
pmc: PMC7457412
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1759720X20943088Informations de copyright
© The Author(s), 2020.
Déclaration de conflit d'intérêts
Conflict of interest statement: Lothar Seefried’s institution (University of Würzburg) received financial support from GSK for participating in this study. Mark Blyth reports no conflicts of interest. Rohit Maheshwari reports no conflicts of interest. Stephen M. McDonnell reports no conflicts of interest. Guillaume Frappin, Martina Hagen, Nadine Maybaum, and Sebastian Moreira are employees of GSK Consumer Healthcare. Hemant Pandit’s institution (University of Leeds) received financial support from GSK for participating in this study.
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