Design: Single-centre, open-label, randomised three-way crossover study
Population: 36 adults aged ≥50 years
Primary outcome: Systemic diclofenac exposure (AUC₀₋₂₄)
Effect: Diethylamine vs sodium gel GMR 90.7% (90% CI 82.7–99.5); exercise 103% (87.8–120.0); heat 92.5% (77.3–111.0)

In this randomised crossover study, 36 adults aged 50 or over applied diclofenac sodium 1% gel, diclofenac diethylamine 1.16% gel, and the sodium gel combined with either heat or moderate exercise, four times daily for seven days each.

Systemic exposure from the two gels was comparable (geometric mean ratio 90.7%). Exercise made no meaningful difference (103%). Heat gave a similar average (92.5%) but a wide interval whose lower bound fell below the standard bioequivalence limit. Urinary excretion was about 0.5% of the applied dose across treatments.

The practical point is the low systemic exposure of topical diclofenac, which underlies its use in older patients for whom oral NSAIDs carry more risk. The study was small and in healthy volunteers, and it measured exposure, not adverse events, so it does not show topical gel is free of systemic effects in people with kidney disease or on anticoagulants.

Prefer topical over oral NSAIDs for localised joint or soft-tissue pain in older adults where suitable.
Either diclofenac salt gives comparable systemic exposure; choose on availability and cost.
Exercise after application did not raise absorption in this study.
Still review use in severe renal impairment, NSAID allergy or with anticoagulants, as large areas or frequent use add up.

Why it matters

It quantifies how little topical diclofenac reaches the circulation, which is the basis of its safety advantage.

The statistics, in plain English

Bioequivalence is judged by whether the 90% confidence interval for the ratio of exposures falls between 80% and 125%. The two gels met that standard; with heat, the interval (77.3–111.0%) dipped below 80%, so the study could not show equivalence, though the average exposure was similar.