Exploratory comparative pharmacokinetic study of a fixed-dose combination of telmisartan/amlodipine/chlorthalidone: half-dose (20/2.5/6.25 mg) versus conventional dose (40/5/12.5 mg)

Low-dose combination therapies are recommended when monotherapy fails to control hypertension.This exploratory study aimed to compare the pharmacokinetics (PK) of 2 fixeddose combinations (FDCs) of telmisartan, amlodipine, and chlorthalidone: half-dose test FDC (20/2.5/6.25 mg) and a conventional-dose reference FDC (40/5/12.5mg).A randomized, open-label, single-dose, parallel-group study was conducted in healthy participants.Each participant received a single oral dose of either the test or reference FDC.Serial blood samples for telmisartan, amlodipine, and chlorthalidone were collected up to 72 hours post-dose, and PK parameters were calculated using noncompartmental analysis.The mean maximum plasma concentrations (C max ) of telmisartan, amlodipine, and chlorthalidone were 41.34 and 155.75 g/L, 1.74 and 4.42 g/L, and 39.36 and 104.86 g/L for the test and reference FDCs, respectively.The mean area under the concentration-time curves to the last measurable time point (AUC last ) were 659.93 and 1673.51hg/L for telmisartan, 57.98 and 128.75 hg/L for amlodipine, and 831.73 and 1826.86 hg/L for chlorthalidone.The test FDC demonstrated systemic exposure levels ranging from 0.27-to 0.39-fold for telmisartan, 0.39-to 0.44-fold for amlodipine, and 0.38-to 0.46-fold for chlorthalidone, compared to the reference FDC.In conclusion, the PK profiles of the half-dose test FDC were consistent with the known characteristics of the individual components.These provide the first PK data for this half-dose test FDC and may support its potential as an alternative treatment option for hypertension.However, as this was an exploratory study, the results should be interpreted with caution.