Design: Randomised, open-label, three-way crossover
Population: 36 adults aged ≥50
Primary outcome: Systemic exposure (AUC0–24)
Effect: Diethylamine vs sodium GMR 90.7% (90% CI 82.7–99.5%)

A single-centre, open-label, randomised three-way crossover study in 36 adults aged 50 or over compared diclofenac sodium 1% gel with diclofenac diethylamine 1.16% gel, each applied four times daily for seven days, and tested the sodium gel with added heat or moderate exercise.

Systemic exposure was comparable between the two salts (geometric mean ratio 90.7%, 90% CI 82.7–99.5%). Exercise did not change absorption (103%, 87.8–120%). Heat gave a similar average but a wider spread, with the lower bound falling below the standard 80% bioequivalence limit (92.5%, 77.3–111%). Only about 0.5% of the dose appeared in urine.

Topical NSAIDs are often chosen for older patients precisely because systemic exposure is low. This study supports treating the two common gel salts as interchangeable on systemic grounds and suggests that heat or activity after application does not raise exposure on average.

The two common topical diclofenac salts gave similar systemic exposure.
Exercise after application did not increase absorption.
Systemic exposure from topical diclofenac is a small fraction of oral dosing, but not zero.
Use the lowest effective amount in patients with renal impairment or on anticoagulants.

Why it matters

It supports topical NSAIDs as a lower-exposure option for older adults without worrying about the salt.

The statistics, in plain English

Bioequivalence is usually declared when the 90% confidence interval for the exposure ratio sits within 80–125%. The heat arm's lower bound dipped to 77%, meaning more variable — not higher — exposure.