Pharmacokinetics and bioequivalence of fixed-dose combination of candesartan cilexetil/amlodipine besylate (16/10 mg) versus coadministration of individual formulations in healthy subjects

Hae Won Lee, Woo Youl Kang, Wookjae Jung, Mi-Ri Gwon, Dong Heon Yang, Eun Hee Kim, Kyunghee Cho, Young-Ran Yoon, Sook Jin Seong, Hae Won Lee, Woo Youl Kang, Wookjae Jung, Mi-Ri Gwon, Dong Heon Yang, Eun Hee Kim, Kyunghee Cho, Young-Ran Yoon, Sook Jin Seong

Abstract

This study compared the pharmacokinetics of a fixed-dose combination (FDC) of candesartan (16 mg) and amlodipine (10 mg) versus coadministration of individual formulations to clarify the bioequivalence of the FDC. In this randomized, open-label, single-dose, 2-treatment, 2-way crossover study, healthy Korean volunteers received a single dose of candesartan (16 mg) with amlodipine (10 mg) as either an FDC or single agents concomitantly administered, with a 2-week washout period. Serial blood samples were collected up to 72 hours after dosing for each treatment period, and plasma concentrations of candesartan and amlodipine were measured using a validated liquid chromatography-tandem mass spectrometry method. A total of 39 subjects completed the study. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0-t) and the peak plasma concentration (Cmax) for candesartan were 1.0182 (0.9562-1.0841) and 0.9492 (0.8726-1.0324), respectively. The GMR and 90% CI for the AUC0-t and Cmax for amlodipine were 1.0552 (1.0255-1.0857) and 1.0668 (1.0259-1.1094), respectively. In conclusion, the new FDC formulation of candesartan (16 mg) and amlodipine (10 mg) was bioequivalent to the concomitant administration of single agents. A single dose of candesartan/amlodipine as the FDC or as single agents was well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT02988362.

Keywords: Amlodipine; Bioequivalence; Candesartan; Hypertension; Pharmacokinetics.

Conflict of interest statement

Conflict of interest: - Authors: Nothing to declare - Reviewers: Nothing to declare - Editors: Nothing to declare

Copyright © 2020 Translational and Clinical Pharmacology.

Figures

Figure 1. Mean (SD) plasma concentration-time profiles…
Figure 1. Mean (SD) plasma concentration-time profiles for (A) candesartan and (B) amlodipine following administration of a single dose of a candesartan/amlodipine (16 mg/10 mg) FDC tablet (○) and individual coadministration of single doses of candesartan (16 mg) and amlodipine (10 mg) (●) in 39 healthy subjects.
SD, standard deviation; FDC, fixed-dose combination.
Figure 2. Mean (A) SBP, (B) DBP,…
Figure 2. Mean (A) SBP, (B) DBP, and (C) PR before (0 hours) and at 6, 8, 24, 36, 48, and 72 hours after administration of a single dose of a candesartan/amlodipine (16 mg/10 mg) FDC tablet (○) and single doses of candesartan (16 mg) and amlodipine (10 mg) individually coadministered (●) in 39 healthy subjects.
SBP, systolic blood pressure; DBP, diastolic blood pressure; PR, pulse rate; FDC, fixed-dose combination.

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