Drug synergism of antihypertensive action in combination of telmisartan with lercanidipine in spontaneous hypertensive rats

Abstract

To examine drug synergism between angiotensin II AT1-receptor blocker and Ca(2+) channel blocker for lowering blood pressure (BP), telmisartan and lercanidipine were orally injected into to telemetered-spontaneous hypertensive rats and BP was monitored. The highest doses of both drugs (7.66 mg/kg of telmisartan and 1.92 mg/kg of lercanidipine) were clinically relevant at 80 and 20 mg human equivalent doses, respectively, and denoted as dose 1. After constructing the dose-response curve using 0 (vehicle-treated control), 1/16, 1/8, 1/4, 1/2 and 1 doses, all possible combinations of both drugs were tested. Drug synergism in combination therapy of telmisartan with lercanidipine was assessed by calculating the interaction index (γ) as evaluated by γ < 1. We found statistically significant drug synergism in the investigated (telmisartan: lercandipine) combinations of (1/8:1/4), (1/4:1) and (1/8:1). Our results suggest that the combination therapy of telmisartan and lercanidipine at lower doses are effective in lowering BP, and also reduce side effects caused by maximal doses of each drug. Therefore, drug combination of AT1-receptor blocker with Ca(2+) channel blocker is a clinically important tool for the management of hypertension and hypertension-related cardiovascular risks.

ANO1 taking center stage: Blood pressure regulation in SHRs

“…In order to reduce side effects of these drugs, or improve the therapeutic efficacy, there have been successful cases of combinatory therapy. For example, combination of telmisartan (AT1R blocker) and lercanidipine (calcium channel blocker) at lower doses are effective in lowering BP, and reducing side effects caused by maximal doses of each drug [28]. Identification of ANO1/VDCC signaling as an important component in blood pressure regulation in the SHRs in particular, may facilitate development of combinatory therapies more effective in attenuating this pathway in essential hypertension.…”