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Effect of food on the oral bioavailability of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide fixed dose combination tablets in healthy subjects

Sunkara, Gangadhar and Jiang, Xuemin and Reynolds, Christine and Serra, Denise and Zhang, Yiming and Ligueros-Saylan, Monica and Ayalasomayajula, Surya and Winter, Serge and Jarugula, Venkateswar (2014) Effect of food on the oral bioavailability of amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide fixed dose combination tablets in healthy subjects. Clinical Pharmacology in Drug Development, 3 (6). pp. 487-492. ISSN 2160763X

Abstract

Amlodipine (calcium channel blocker), valsartan (angiotensin receptor blocker) and hydrochlorothiazide (HCTZ, a diuretic) are antihypertensive drugs available as monotherapies. A double fixed dose combination of amlodipine/valsartan and triple fixed dose combination of amlodipine/valsartan/HCTZ tablets have been developed to treat patients with moderate to severe hypertension. In this paper, the effect of food on the oral bioavailability of these two fixed dose combination tablets is presented. Two separate clinical studies were conducted in healthy subjects with each fixed dose combination product using a randomized, open-label, two-period crossover study design with a washout period of at least 14 days. In the study with amlodipine/valsartan combination tablet, a total of 37 healthy male and female subjects received a single 10/160 mg oral dose under fasted or fed conditions. In the study of amlodipine/valsartan/HCTZ tablet, a total of 35 subjects received a single 10/320/25 mg oral dose under fasted or fed conditions. Blood samples were collected at pre-determined time points (predose and up to 168 hours post-dose) in both studies to determine amlodipine, valsartan and/or HCTZ concentrations in plasma simultaneously by a validated LC/MS/MS methods. The PK parameters tmax, Cmax, AUC0-t and AUC0-∞ of these analytes were estimated by non-compartmental analysis. The study results were interpreted based on geometric mean ratios (90% CI) between fed and fasted conditions. Following single dose oral administration of 10/160 mg amlodipine/valsartan fixed combination tablet, amlodipine and valsartan AUCs were comparable between the fed and fasting conditions while the valsartan Cmax was decreased slightly by 14% under fed conditions. The bioavailability of amlodipine, valsartan and HCTZ was similar under fed and fasting conditions following a single dose oral administration of 10/320/25 mg amlodipine/valsartan/HCTZ fixed combination tablet. In conclusion, both fixed dose combination tablets can be administered without regards to meals.
Key Words: Amlodipine, valsartan and hydrochlorothiazide (HCTZ), fixed dose combination, food effect

Item Type: Article
Date Deposited: 12 Oct 2016 00:45
Last Modified: 12 Oct 2016 00:45
URI: https://oak.novartis.com/id/eprint/9362

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