Key result
Telmisartan plus hydrochlorothiazide shows synergistic blood pressure reduction in a hypertensive rat model.
Why the study?
Does the combination of telmisartan and hydrochlorothiazide have a synergistic antihypertensive effect in spontaneously hypertensive rats?
Does the combination of telmisartan and hydrochlorothiazide have a synergistic antihypertensive effect in spontaneously hypertensive rats?
A pharmacokinetic-pharmacodynamic model demonstrates a synergistic antihypertensive interaction between telmisartan and hydrochlorothiazide in spontaneously hypertensive rats.
Establishes PK-PD model for telmisartan-HCTZ interaction in rats; leaves open translation to human hypertension therapy.
OBJECTIVES: The goal of this study was to establish an integrated indirect response pharmacokinetic-pharmacodynamic model between telmisartan and hydrochlorothiazide to describe the antihypertensive interaction of these two drugs in spontaneously hypertensive rats. METHODS: The blood pressure and plasma concentrations were measured by the tail-cuff test and high performance liquid chromatography-mass spectrometry, respectively, in spontaneously hypertensive rats. The current pharmacokinetic-pharmacodynamic model was based on the non-competitive pharmacodynamic interaction of two drugs acting on different physiological processes. KEY FINDINGS: This model was able to acquire the temporal changes in drug concentration and blood pressure after administration of telmisartan or hydrochlorothiazide. The noncompetitive pharmacodynamic interaction assumed that the decreased blood pressure was attributed to the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after administration of these two drugs. There was no significant pharmacokinetic change of telmisartan and hydrochlorothiazide in the different groups tested. The model predicted a synergistic pharmacodynamic interaction when telmisartan was administered in combination with hydrochlorothiazide, which was notably stronger than if the effects were additive. CONCLUSION: The results showed that the presented pharmacokinetic-pharmacodynamic model was suitable for describing the antihypertensive interaction between telmisartan and hydrochlorothiazide.
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Hao et al. (2014) studied Hypertension. Telmisartan and hydrochlorothiazide combination vs. Telmisartan or hydrochlorothiazide alone was evaluated on Blood pressure and plasma concentrations. A pharmacokinetic-pharmacodynamic model in spontaneously hypertensive rats predicted a synergistic antihypertensive interaction between telmisartan and hydrochlorothiazide.
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