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

Arch Pharm Res. 2010 Sep;33(9):1411-8. doi: 10.1007/s12272-010-0915-9. Epub 2010 Oct 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / therapeutic use*
  • Benzoates / administration & dosage
  • Benzoates / therapeutic use*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / therapeutic use*
  • Dihydropyridines / administration & dosage
  • Dihydropyridines / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Heart Rate / drug effects
  • Hypertension / drug therapy*
  • Kinetics
  • Male
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Statistics as Topic
  • Telmisartan

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Benzimidazoles
  • Benzoates
  • Calcium Channel Blockers
  • Dihydropyridines
  • Telmisartan
  • lercanidipine