Evaluation of a Pharmacokinetic Interaction between Telmisartan and Chlorthalidone in Healthy Male Adult Subjects.

Abstract

Combination therapy is recommended for the effective management of hypertension according to most treatment guidelines, including those of the US Joint National Committee. Therefore, pharmacokinetic drug interactions are an important issue in combination therapy for hypertension. In this study, the pharmacokinetic properties of telmisartan and chlorthalidone were evaluated to investigate their pharmacokinetic interactions in healthy subjects. Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted. In study A, 43 participants received 80mg of telmisartan orally for 7days, and were then administered oral chlorthalidone 25mg for 14days (days 8-21), coadministered with 80mg of telmisartan from day 15. In study B, 14 participants received oral chlorthalidone (25mg) for 13days, followed by coadministration with 80mg of telmisartan orally for 7days. The geometric mean ratios (GMRs) (90% confidence intervals [CIs]) of the maximum plasma concentration (C max,ss) and area under the concentration-time curve for the dosing interval at steady state (AUCτ,ss) of telmisartan (with and without chlorthalidone) were 1.018 (0.861-1.203) and 1.099 (1.015-1.190), respectively. For chlorthalidone (with/without telmisartan), the GMRs (90% CIs) for C max,ss and AUCτ,ss were 0.996 (0.922-1.075) and 0.992 (0.925-1.064), respectively. The GMRs and 90% CIs for telmisartan and chlorthalidone were all within the 0.80-1.25 range. Thus, in this study, there was no significant pharmacokinetic interaction between telmisartan and chlorthalidone. CLINICALTRIAL. NCT01806363.