Quantifying pharmacodynamic interaction between atenolol and valsartan

Abstract

Abstract We used mathematical modeling in order to determine the pharmacodynamic relationship between antihypertensive drugs atenolol and valsartan, by evaluating their effects on heart rate (HR), systolic blood pressure (SP) and diastolic blood pressure (DP). A group of twelve healthy male volunteers received a single oral dose of 100 mg of atenolol and 160 mg of valsartan, both separately and in combination. Pharmacokinetic (PK), pharmacokinetic/pharmacodynamic (PK/PD) and pharmacodynamic (PD) systems were proposed and PD model of atenolol and valsartan concentration-time profiles and PK/PD model of blood pressure and heart rate effects after administration of single doses of atenolol and valsartan and their combination were constructed. Parameters of PD system, such as gain and mean effect time, were obtained by analysis of PK and PK/PD systems. Modeling of PK and PK/PD systems and their analysis to obtain the PD results could considerably change the view o treatment of individual diseases in terms of greater knowledge of pharmacokinetics and pharmacodynamics of drugs.