Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study

Abstract

Background: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is an investigational formulation that uses dispersing agents designed to facilitate rapid and consistent absorption of this NSAID.

Objective: The aim of this study was to characterize the effects of food intake on the pharmacokinetic (PK) profile of oral DPSGC at doses of 25 and 50 mg.

Methods: In this open-label, randomized, single-dose (2 distinct doses), 2-way crossover bioavailability study, healthy adult volunteers were randomly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast (fasted condition) or high-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 6 hours after study drug administration. Concentrations of diclofenac in plasma were determined using HPLC, and PK profiles were studied using ANCOVA. Adverse events (AEs) were monitored and recorded on each in-clinic day.

Results: Of 47 participants included in the study, 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose. The majority of participants were male (80.9%), and the mean age was 28.6 years. The mean (SD) AUC values for the fasted and fed states were 691 (195) and 680 (184) ng x h/mL, respectively, with the 25-mg dose, and 1521 (377) and 1416 (366) ng . h/mL, respectively, with the 50-mg dose, suggesting that the extent of absorption was similar with both dietary conditions at each dose. Food intake was associated with decreases in C(max) by nearly half in the 25-mg group (fasted vs fed, 1156 [482] vs 686 [411] ng/mL, respectively; P < 0.05) and the 50-mg group (2365 [1034] vs 1154 [592 ng/mL; P < 0.05) and delayed T(max) in the 25-mg group (0.49 [0.16] vs 1.02 [0.55] hours; P < 0.05) and 50-mg group (0.51 [0.19] vs 1.28 [0.71] hours; P < 0.05). Two mild AEs (nasal congestion and light-headedness) were reported in 2 participants who received 25 mg under fed conditions and 50 mg under fasted conditions, respectively.

Conclusions: Food intake did not appear to affect the extent of absorption (ie, total exposure) of oral DPSGC at doses of 25 and 50 mg in these healthy adult volunteers. Both single doses appeared to be well tolerated.