TTOXICOLOGICAL EVALUATION OF COMBINATION OF AMLODIPINE CALCIUM CHANNELS BLOCKER WITH ANGIOTENSIN RECEPTOR BLOCKERS

Abstract

The article summarizes experimental data on toxicological interactions of blocker of amplodipine slow calcium channels with angiotensin II (AT1 subtype) receptors blockers (valsartan and losartan). Toxicity studies were performed in outbred rats after a single intragastric administration in doses permitting to estimate lethal doses for the objects under investigation (amlodipine, valsartan, losartan, amlodipine+ losartan 1:10, amlodipine+ losartan 1:20, amlodipine + valsartan 1:16, amlodipine + valsartan 1:32). Based on the research outcome, the possibility of different types of toxicological interaction is shown between representatives of classes of slow calcium channels blockers and angiotensin II receptors blockers: from potentiation of toxic effects to the antagonism in relation to toxicity. Identified toxicological interactions in fixed combinations depend on the proportion of active ingredients in the combination, as well as on modes of action features and pharmacokinetics of each active ingredient.