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).

UNLABELLED: Low-dose combination therapies are recommended when monotherapy fails to control hypertension. This exploratory study aimed to compare the pharmacokinetics (PK) of 2 fixed-dose combinations (FDCs) of telmisartan, amlodipine, and chlorthalidone: half-dose test FDC (20/2.5/6.25 mg) and a conventional-dose reference FDC (40/5/12.5 mg). 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 (Cmax) of telmisartan, amlodipine, and chlorthalidone were 41.34 and 155.75 μg/L, 1.74 and 4.42 μg/L, and 39.36 and 104.86 μg/L for the test and reference FDCs, respectively. The mean area under the concentration-time curves to the last measurable time point (AUClast) were 659.93 and 1,673.51 h·μg/L for telmisartan, 57.98 and 128.75 h·μg/L for amlodipine, and 831.73 and 1,826.86 h·μg/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.

TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0010166.