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Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants.
Int J Clin Pharmacol Ther. 2015 Mar; 53(3):256-64.IJ

Abstract

OBJECTIVE

To assess the effect of food on the pharmacokinetics (PK) of canagliflozin and metformin following administration of a canagliflozin/metformin (150/1,000 mg) immediate-release (IR) fixed-dose combination (FDC) tablet.

METHODS

A randomized, open-label, singlecenter, single-dose, 2-period, 2-sequence crossover study was conducted in healthy participants. Participants were randomized to 2 sequences of fasted and fed (or vice versa) administration of one 150/1,000 mg canagliflozin/metformin IR FDC, with 10-14 day washout between treatments PK parameters (AUC, Cmax, tmax, t1/2) were assessed for canagliflozin and metformin. Safety was evaluated.

RESULTS

When comparing the IR FDC tablet administered with and without food, PK parameters of canagliflozin were bioequivalent as the 90% confidence intervals (CIs) for log-transformed AUClast, AUCâ-쎗, and Cmax were within the bioequivalence limits of 80-125%. For metformin, overall exposure was similar under fed and fasted conditions as geometric mean ratios for AUC and associated 90% CI were contained within the bioequivalence limits, but geometric mean Cmax decreased by 16% in the fed compared to fasted state. Both treatments were well tolerated with similar adverse events and most common were gastrointestinal events, generally attributed to metformin.

CONCLUSIONS

Food did not affect canagliflozin bioavailability parameters (Cmax and AUCs) or AUCs of metformin. The Cmax of metformin was decreased by 16%, which is not considered clinically meaningful. The canagliflozin/metformin FDC tablet is recommended to be taken with meals to reduce the symptoms of gastrointestinal intolerability associated with metformin.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25546166

Citation

Murphy, Joseph, et al. "Effect of Food On the Pharmacokinetics of Canagliflozin/metformin (150/1,000 Mg) Immediate-release Fixed-dose Combination Tablet in Healthy Participants." International Journal of Clinical Pharmacology and Therapeutics, vol. 53, no. 3, 2015, pp. 256-64.
Murphy J, Wang SS, Stieltjes H, et al. Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants. Int J Clin Pharmacol Ther. 2015;53(3):256-64.
Murphy, J., Wang, S. S., Stieltjes, H., Wajs, E., & Devineni, D. (2015). Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants. International Journal of Clinical Pharmacology and Therapeutics, 53(3), 256-64. https://doi.org/10.5414/CP202233
Murphy J, et al. Effect of Food On the Pharmacokinetics of Canagliflozin/metformin (150/1,000 Mg) Immediate-release Fixed-dose Combination Tablet in Healthy Participants. Int J Clin Pharmacol Ther. 2015;53(3):256-64. PubMed PMID: 25546166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants. AU - Murphy,Joseph, AU - Wang,Shean-Sheng, AU - Stieltjes,Hans, AU - Wajs,Ewa, AU - Devineni,Damayanthi, PY - 2015/02/23/accepted PY - 2014/12/30/entrez PY - 2014/12/30/pubmed PY - 2015/8/19/medline SP - 256 EP - 64 JF - International journal of clinical pharmacology and therapeutics JO - Int J Clin Pharmacol Ther VL - 53 IS - 3 N2 - OBJECTIVE: To assess the effect of food on the pharmacokinetics (PK) of canagliflozin and metformin following administration of a canagliflozin/metformin (150/1,000 mg) immediate-release (IR) fixed-dose combination (FDC) tablet. METHODS: A randomized, open-label, singlecenter, single-dose, 2-period, 2-sequence crossover study was conducted in healthy participants. Participants were randomized to 2 sequences of fasted and fed (or vice versa) administration of one 150/1,000 mg canagliflozin/metformin IR FDC, with 10-14 day washout between treatments PK parameters (AUC, Cmax, tmax, t1/2) were assessed for canagliflozin and metformin. Safety was evaluated. RESULTS: When comparing the IR FDC tablet administered with and without food, PK parameters of canagliflozin were bioequivalent as the 90% confidence intervals (CIs) for log-transformed AUClast, AUCâ-쎗, and Cmax were within the bioequivalence limits of 80-125%. For metformin, overall exposure was similar under fed and fasted conditions as geometric mean ratios for AUC and associated 90% CI were contained within the bioequivalence limits, but geometric mean Cmax decreased by 16% in the fed compared to fasted state. Both treatments were well tolerated with similar adverse events and most common were gastrointestinal events, generally attributed to metformin. CONCLUSIONS: Food did not affect canagliflozin bioavailability parameters (Cmax and AUCs) or AUCs of metformin. The Cmax of metformin was decreased by 16%, which is not considered clinically meaningful. The canagliflozin/metformin FDC tablet is recommended to be taken with meals to reduce the symptoms of gastrointestinal intolerability associated with metformin. SN - 0946-1965 UR - https://www.unboundmedicine.com/medline/citation/25546166/Effect_of_food_on_the_pharmacokinetics_of_canagliflozin/metformin__150/1000_mg__immediate_release_fixed_dose_combination_tablet_in_healthy_participants_ L2 - http://www.dustri.com/nc/journals-in-english?artId=12996 DB - PRIME DP - Unbound Medicine ER -