Effects of Food Intake on the Pharmacokinetics of Azilsartan Medoxomil and Chlorthalidone Alone and in Fixed-Dose Combination in Healthy Adults
Caroline Dudkowski, Aziz Karim, Melvin Munsaka, Caroline Dudkowski, Aziz Karim, Melvin Munsaka
Abstract
Azilsartan medoxomil is a long-acting angiotensin II receptor blocker used to treat hypertension as monotherapy or in fixed-dose combination (FDC) with chlorthalidone. This study assessed the effects of food intake on the plasma pharmacokinetics of the active moiety, azilsartan, and of chlorthalidone when administered as separate tablets or in FDC. Cohort 1 (n = 24) received azilsartan medoxomil (80 mg) and chlorthalidone (25 mg) once in a fasted condition and once 30 minutes after the initiation of a high-fat meal (fed). Cohort 2 (n = 24) received the same drugs as an FDC tablet in the fasted and fed conditions. In cohort 1, the fed-fasted ratios for AUC0-inf and Cmax were 108.3 (101.6-115.5) and 103.7 (94.3-114.1), respectively, for azilsartan and 112.3 (106.5-118.4) and 100.3 (90.6-111.1), respectively, for chlorthalidone. In cohort 2, the corresponding ratios were 78.6 (67.6-91.4) and 78.6 (64.4-96.0) for azilsartan and 101.0 (96.5-86.7) and 75.9 (66.5-86.7) for chlorthalidone. The combination therapies were well tolerated, and food intake had no consistent effect on adverse events. Food intake had a somewhat greater effect on plasma pharmacokinetics after administration of the FDC tablet than after administration of separate tablets, but the effects of food on the plasma pharmacokinetics of the FDC were not expected to be clinically meaningful.
Keywords: AUC; Cmax; angiotensin II receptor blocker; half-life; hypertension.
© 2016, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.
Figures
References
- Perry CM. Azilsartan medoxomil: a review of its use in hypertension. Clin Drug Investig. 2012;32(9):621–639.
- Ernst ME, Carter BL, Goerdt CJ, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 2006;47(3):352–358.
- Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. 2011;57(4):689–694.
- Wright JT, Jr. , Probstfield JL, Cushman WC, et al. ALLHAT findings revisited in the context of subsequent analyses, other trials, and meta‐analyses. Arch Intern Med. 2009;169(9):832–842.
- Sica D, Bakris GL, White WB, Weber MA, Cushman WC, Huang P, et al. Blood pressure‐lowering efficacy of the fixed‐dose combination of azilsartan medoxomil and chlorthalidone: a factorial study. J Clin Hypertens (Greenwich). 2012;14(5):284–292.
- Cushman WC, Bakris GL, White WB, Weber MA, Sica D, Roberts A, et al. Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension. Hypertension 2012;60(2):310–318.
- Pierini D, Anderson KV. Azilsartan medoxomil/chlorthalidone: a new fixed‐dose combination antihypertensive. Ann Pharmacother. 2013;47(5):694–703.
- Harrell RE, Karim A, Zhang W, Dudkowski C. Effects of age, sex, and race on the safety and pharmacokinetics of single and multiple doses of azilsartan medoxomil in healthy subjects [published online ahead of print 2015]. Clin Pharmacokinet.
- Cheng JW. Azilsartan/chlorthalidone combination therapy for blood pressure control. Integr Blood Press Control. 2013;6:39–48.
- Jauregui‐Garrido B, Jauregui‐Lobera I. Interactions between antihypertensive drugs and food. Nutr Hosp. 2012;27(6):1866–1875.
Source: PubMed