Key result
Amlodipine combined with telmisartan or candesartan demonstrates optimal synergistic blood pressure reduction.
Why the study?
The synergistic effects of amlodipine combined with telmisartan or candesartan on blood pressure reduction in vivo were not fully evaluated using advanced synergy analysis methods.
Does the combination of amlodipine and telmisartan or candesartan produce synergistic blood pressure reduction in spontaneously hypertensive rats?
Does the combination of amlodipine and telmisartan or candesartan produce synergistic blood pressure reduction in spontaneously hypertensive rats?
This study demonstrates that amlodipine synergizes with telmisartan or candesartan to optimally reduce blood pressure in vivo, and validates SynergyFinder 3.0 as a reliable tool for assessing in vivo drug synergy.
Animal data on amlodipine-ARB synergy should not change practice; leaves open translation and further SynergyFinder validation in clinical settings.
This study was designed to evaluate the synergism of two couples of antihypertensive drugs (amlodipine + telmisartan and amlodipine + candesartan) on blood pressure reduction in vivo by both SynergyFinder 3.0 and probability sum test. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (0.5, 1, 2, and 4 mg/kg), telmisartan (4, 8, and 16 mg/kg), candesartan (1, 2, and 4 mg/kg), nine combinations for amlodipine and telmisartan, and nine combinations for amlodipine and candesartan. The control rats were treated by 0.5% carboxymethylcellulose sodium. Blood pressure was recorded continuously up to 6 h after administration. Both SynergyFinder 3.0 and the probability sum test were used to evaluate the synergistic action. The synergisms calculated by SynergyFinder 3.0 are consistent with the probability sum test both in two different combinations. There is an obviously synergistic interaction between amlodipine and telmisartan or candesartan. The combinations of amlodipine and telmisartan (2 + 4 and 1 + 4 mg/kg) and amlodipine and candesartan (0.5 + 4 and 2 + 1 mg/kg) might exert an optimum synergism against hypertension. Compared with the probability sum test, SynergyFinder 3.0 is more stable and reliable to analyze the synergism.
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Xia et al. (2023) studied Hypertension (Spontaneously Hypertensive Rats) (n=290). Amlodipine combined with telmisartan or candesartan vs. Vehicle control (0.5% carboxymethylcellulose sodium) and monotherapies was evaluated on Synergism on blood pressure reduction (SBP, DBP, MBP). Combinations of amlodipine and telmisartan or candesartan exerted optimal synergism against hypertension, with SynergyFinder 3.0 proving more stable than the probability sum test for in vivo evaluation.
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