Differential Pharmacokinetics of Diclofenac Potassium for Oral Solution vs Immediate‐Release Tablets From a Randomized Trial: Effect of Fed and Fasting Conditions

Abstract

Diclofenac potassium oral solution and tablet formulations produced statistically significantly different Cmax and tmax but similar AUC under fed and fasting conditions. Fed conditions produced significantly lower Cmax for both formulations and profoundly delayed tmax for the tablet, but had no effect on tmax for the solution formulation. These data provide insights into the importance of an earlier and greater exposure to diclofenac arising from the solution formulation than the tablet, which may account for the superiority in the onset and sustained pain reduction for the solution than the tablet formulation observed in the double-blind, efficacy/safety study in migraine patients conducted in Europe.

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging†

“…The different gastric acidity in fasted and fed conditions might lead to differences in oral drug dissolution and the speed of precipitation within the gastrointestinal tract . Correspondingly, the peak plasma concentration of diclofenac under fed conditions was reported to be significantly lower and the time to peak plasma concentration was significantly longer compared to fasted conditions . The state of food intake was not standardized in our study, which might have altered absorption and bioavailability rates of diclofenac.…”

“…[32] Correspondingly, the peak plasma concentration of diclofenac under fed conditions was reported to be significantly lower and the time to peak plasma concentration was significantly longer compared to fasted conditions. [23] The state of food intake was not standardized in our study, which might have altered absorption and bioavailability rates of diclofenac. Other influencing factors on diclofenac metabolism and pharmacokinetics are interethnic variability of CYP450 2C9 genotypes, which is responsible for the first-pass metabolism of diclofenac [33,34] as well as different concentrations of plasma binding proteins.…”

“…24/24 healthy volunteers received a single oral dose of 50 mg diclofenac sodium (Voltaren ® ; GlaxoSmithKline, Munich, Germany) and underwent the second MRI 60–100 min afterwards. The time point was chosen according to previous reports that plasma concentration peaks 60–100 min after oral application …”

“…The time point was chosen according to previous reports that plasma concentration peaks 60-100 min after oral application. [8,22,23] Twelve of 24 participants were examined after topical application of diclofenac (Voltaren Emulgel Gel, 1.16%) over 3 days (three applications per day). Participants were instructed to cover an area of the skin of 210 9 297 mm (DIN A4, e.g.…”

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“…Kehlet et al, proposed that the combination of opioids and NSAIDs which has additive analgesic action reduces postoperative pain more effectively than the single drug therapy. Chen C et al, found that the combination therapy with tramadol and diclofenac resulted in significant improvement in postoperative pain relief than monotherapy with tramadol and diclofenac 14 .…”