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.

Abstract

Management of hypertension and hyperlipidemia is important to reduce the risk of cardiovascular disease, and a fixed-dose combination (FDC) of antihypertensive and lipid-lowering 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.

Trial registration: ClinicalTrials.gov Identifier: NCT04611932.