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Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study.
Clin Ther. 2009 Oct; 31(10):2233-41.CT

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.

Authors+Show Affiliations

AAI Human Pharmacology Center, Chapel Hill, North Carolina, USA. ralph.scallion@gmail.comNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19922894

Citation

Scallion, Ralph, and Keith A. Moore. "Effects of Food Intake On the Pharmacokinetics of Diclofenac Potassium Soft Gelatin Capsules: a Single-dose, Randomized, Two-way Crossover Study." Clinical Therapeutics, vol. 31, no. 10, 2009, pp. 2233-41.
Scallion R, Moore KA. Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study. Clin Ther. 2009;31(10):2233-41.
Scallion, R., & Moore, K. A. (2009). Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study. Clinical Therapeutics, 31(10), 2233-41. https://doi.org/10.1016/j.clinthera.2009.10.001
Scallion R, Moore KA. Effects of Food Intake On the Pharmacokinetics of Diclofenac Potassium Soft Gelatin Capsules: a Single-dose, Randomized, Two-way Crossover Study. Clin Ther. 2009;31(10):2233-41. PubMed PMID: 19922894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study. AU - Scallion,Ralph, AU - Moore,Keith A, PY - 2009/07/17/accepted PY - 2009/11/20/entrez PY - 2009/11/20/pubmed PY - 2010/1/27/medline SP - 2233 EP - 41 JF - Clinical therapeutics JO - Clin Ther VL - 31 IS - 10 N2 - 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. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/19922894/Effects_of_food_intake_on_the_pharmacokinetics_of_diclofenac_potassium_soft_gelatin_capsules:_a_single_dose_randomized_two_way_crossover_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(09)00346-4 DB - PRIME DP - Unbound Medicine ER -