What is the clinical evidence from this study?

Study design: RCT. Population: Healthy subjects (n=51). Intervention: Candesartan/amlodipine/atorvastatin fixed-dose combination vs. Separate tablets of candesartan/amlodipine (8/5 mg) and atorvastatin (10 mg). Primary outcome: Pharmacokinetic equivalence (AUCt and Cmax) (GMR 0.9360-1.0658, 95% CI 0.8885-1.2123).

April 1, 2026Open Access

Comparative pharmacokinetics of a candesartan/amlodipine/atorvastatin fixed-dose combination 8 mg/5 mg/10 mg versus separate tablets in healthy subjects: a partial replicated crossover study

Key Result

The fixed-dose combination of candesartan 8 mg, amlodipine 5 mg, and atorvastatin 10 mg demonstrated pharmacokinetic equivalence to separate tablets, with all 90% confidence intervals within limits.

Key Points

This study aims to compare the pharmacokinetics of a fixed-dose combination of candesartan, amlodipine, and atorvastatin against their separate formulations.
Conducted as a randomized, open-label, single-dose, 2-treatment, 3-sequence, 3-period study
51 healthy subjects participated, taking either fixed-dose combination or separate tablets
Blood samples were collected up to 72 hours after dosing
Pharmacokinetic parameters were analyzed using noncompartmental analysis
LC-MS/MS method was used to assay plasma concentrations of the drugs.
43 subjects were included for pharmacokinetic analysis of candesartan and atorvastatin, while 42 for amlodipine
Geometric mean ratios for candesartan's area under the curve were 0.9637 and maximum plasma concentration was 0.9360
Mean ratios for amlodipine were 0.9694 and 0.9930 respectively
Atorvastatin showed ratios of 1.0350 for area under the curve and 1.0658 for maximum plasma concentration
The findings suggest pharmacokinetic equivalence between fixed-dose combination and separate tablets.

Study Design

Type

RCT (n=51)

Blinding

Open-label

Randomization

Randomized, 3-sequence, 3-period partial replicated crossover

Multicenter

Structured PICO

Does a fixed-dose combination of candesartan 8 mg, amlodipine 5 mg, and atorvastatin 10 mg show pharmacokinetic equivalence to separate tablets in healthy subjects?

Population

51 healthy Korean adult volunteers aged 19–54 years, BMI 17.5-30.5 kg/m2. Mean age 26.69, 84% male (43/51).

Intervention

Single dose of fixed-dose combination (FDC) tablet containing candesartan 8 mg, amlodipine 5 mg, and atorvastatin 10 mg

Comparator

Single dose of separate tablets: candesartan/amlodipine FDC (8/5 mg) and atorvastatin (10 mg)

Outcome

Pharmacokinetic equivalence based on area under the plasma concentration-time curve from time zero to the last sampling time (AUCt) and maximum plasma concentration (Cmax) up to 72 hours post-dosesurrogate

The fixed-dose combination of candesartan, amlodipine, and atorvastatin is pharmacokinetically equivalent to its separate components, offering a potential strategy to reduce pill burden in patients with hypertension and hyperlipidemia.

Main Result

Effect estimate: GMR 0.9360-1.0658 (95% CI 0.8885-1.2123)

Limitations

Conducted in healthy adult volunteers rather than the target patient population with hypertension and hyperlipidemia.
Focused on single-dose pharmacokinetics under fasting conditions, which does not fully capture steady-state dynamics.
Not designed to measure long-term clinical outcomes such as blood pressure reduction or lipid-lowering effects.

Abstract

Management of hypertension and hyperlipidemia is important to reduce the risk of cardiovascular disease, and a fixed-dose combination (FDC) of antihypertensive and lipidlowering drugs is expected to reduce the pill burden and increase patient compliance.The aim of this study was to compare the pharmacokinetics (PKs) of candesartan, amlodipine, and atorvastatin FDC versus separate tablets.A randomized, open-label, single-dose, 2-treatment, 3-sequence, 3-period, partial replicated crossover study was conducted in healthy subjects.A total of 51 subjects were randomized into 1 of 3 sequences and received a single dose of either an FDC or separate tablets of candesartan 8 mg, amlodipine 5 mg, and atorvastatin 10 mg, with a 14-day washout period in between.Plasma samples were collected up to 72 hours after dosing.Plasma concentrations of candesartan, amlodipine and atorvastatin were assayed using a validated LC-MS/MS method, and PK parameters were determined by noncompartmental analysis.As a result, 43 subjects were included in PK analysis for candesartan, atorvastatin, and 42 subjects were included in PK analysis for amlodipine.The geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from time zero to the last sampling time and maximum plasma concentration were 0.9637 (0.9192-1.0104) and 0.9360 (0.8885-0.9861) for candesartan, 0.9694 (0.9417-0.9978) and 0.9930 (0.9575-1.0299) for amlodipine, and 1.0350 (0.9891-1.0831) and 1.0658 (0.9370-1.2123) for atorvastatin, respectively.This study suggested that the FDC formulation of candesartan, amlodipine, and atorvastatin showed PK equivalence compared to separate tablets.

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