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Oral antidiabetic drugs: effect of food on absorption of pioglitazone and metformin from a fixed-dose combination tablet.
J Clin Pharmacol. 2007 Jan; 47(1):48-55.JC

Abstract

An open-label, randomized, crossover study involving 28 healthy subjects was conducted to compare the peak (Cmax) and total (AUC(lqc), AUC(infinity)) exposures to pioglitazone and metformin after single-dose administration of a fixed-dose combination tablet containing 15 mg of pioglitazone plus 850 mg metformin when given under fasted versus fed states, with a washout period of 7 days between treatments. Two different fixed-dose combination formulations (bilayer and pioglitazone-micronized fixed-dose combination tablets) were tested. The pioglitazone-micronized fixed-dose combination formulation was selected for clinical development and regulatory approval; the present study describes food effect results with this formulation. For pioglitazone, least squares mean ratios (fed/fasted) and the 90% confidence intervals of these ratios were 1.05 (0.93-1.18) for Cmax, 1.13 (1.02-1.25) for AUC(lqc), and 1.11 (1.01-1.22) for AUC(infinity). For metformin, these values were 0.72 (0.65-0.79) for Cmax, 0.87 (0.81-0.94) for AUC(lqc), and 0.87 (0.81-0.94) for AUC(infinity). Dosing with food resulted in median prolongation of tmax values by 1.5 hours for metformin and 2.0 hours for pioglitazone. Because bioequivalency criteria were met (fed/fasted 90% confidence interval between 0.80 and 1.25) for both pioglitazone and metformin AUC, fixed-dose combination tablets can be taken with or without food, but to minimize gastrointestinal adverse effects of metformin, the fixed-dose combination tablets are recommended to be taken with food.

Authors+Show Affiliations

Takeda Global Research & Development Center, Inc, 475 Half Day Road, Lincolnshire, IL 60069, USA. akarim@tgrd.comNo 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

17192501

Citation

Karim, Aziz, et al. "Oral Antidiabetic Drugs: Effect of Food On Absorption of Pioglitazone and Metformin From a Fixed-dose Combination Tablet." Journal of Clinical Pharmacology, vol. 47, no. 1, 2007, pp. 48-55.
Karim A, Slater M, Bradford D, et al. Oral antidiabetic drugs: effect of food on absorption of pioglitazone and metformin from a fixed-dose combination tablet. J Clin Pharmacol. 2007;47(1):48-55.
Karim, A., Slater, M., Bradford, D., Schwartz, L., & Laurent, A. (2007). Oral antidiabetic drugs: effect of food on absorption of pioglitazone and metformin from a fixed-dose combination tablet. Journal of Clinical Pharmacology, 47(1), 48-55.
Karim A, et al. Oral Antidiabetic Drugs: Effect of Food On Absorption of Pioglitazone and Metformin From a Fixed-dose Combination Tablet. J Clin Pharmacol. 2007;47(1):48-55. PubMed PMID: 17192501.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral antidiabetic drugs: effect of food on absorption of pioglitazone and metformin from a fixed-dose combination tablet. AU - Karim,Aziz, AU - Slater,Margaret, AU - Bradford,Dawn, AU - Schwartz,Lisa, AU - Laurent,Aziz, PY - 2006/12/29/pubmed PY - 2007/3/3/medline PY - 2006/12/29/entrez SP - 48 EP - 55 JF - Journal of clinical pharmacology JO - J Clin Pharmacol VL - 47 IS - 1 N2 - An open-label, randomized, crossover study involving 28 healthy subjects was conducted to compare the peak (Cmax) and total (AUC(lqc), AUC(infinity)) exposures to pioglitazone and metformin after single-dose administration of a fixed-dose combination tablet containing 15 mg of pioglitazone plus 850 mg metformin when given under fasted versus fed states, with a washout period of 7 days between treatments. Two different fixed-dose combination formulations (bilayer and pioglitazone-micronized fixed-dose combination tablets) were tested. The pioglitazone-micronized fixed-dose combination formulation was selected for clinical development and regulatory approval; the present study describes food effect results with this formulation. For pioglitazone, least squares mean ratios (fed/fasted) and the 90% confidence intervals of these ratios were 1.05 (0.93-1.18) for Cmax, 1.13 (1.02-1.25) for AUC(lqc), and 1.11 (1.01-1.22) for AUC(infinity). For metformin, these values were 0.72 (0.65-0.79) for Cmax, 0.87 (0.81-0.94) for AUC(lqc), and 0.87 (0.81-0.94) for AUC(infinity). Dosing with food resulted in median prolongation of tmax values by 1.5 hours for metformin and 2.0 hours for pioglitazone. Because bioequivalency criteria were met (fed/fasted 90% confidence interval between 0.80 and 1.25) for both pioglitazone and metformin AUC, fixed-dose combination tablets can be taken with or without food, but to minimize gastrointestinal adverse effects of metformin, the fixed-dose combination tablets are recommended to be taken with food. SN - 0091-2700 UR - https://www.unboundmedicine.com/medline/citation/17192501/Oral_antidiabetic_drugs:_effect_of_food_on_absorption_of_pioglitazone_and_metformin_from_a_fixed_dose_combination_tablet_ L2 - https://doi.org/10.1177/0091270006293756 DB - PRIME DP - Unbound Medicine ER -