Pharmacokinetic and Pharmacodynamic Profile of Nebivolol in an Animal Model of Metabolic Syndrome

Abstract

The cardiovascular and pharmacokinetic effects of nebivolol were evaluated in hypertensive fructose-fed and control rats,analyzing the effect of intravenously administered nebivolol 3 or 10 mg/kg on blood pressure, heart rate, and short-term andbeat-to-beat blood pressure variability. The enantioselective pharmacokinetic profile of d- and l-nebivolol enantiomers wasevaluated. Short-term and beat-to-beat blood pressure variability was assessed using standard deviation and blood pressurespectral analysis, respectively. The hypertensive state altered the pharmacokinetics of nebivolol, evidenced by reduction ofnebivolol clearance in the fructose group compared to the control group after administration of the highest dose. The antihypertensiveeffect of nebivolol was similar in both groups, while the bradycardic effect was greater in control rats. Althoughno significant differences were found in beat-to-beat blood pressure variability, short-term blood pressure variability showedgreater reduction after nebivolol administration in fructose-fed rats compared to control normotensive animals (-57.9%±11.8%vs.-19.6%±9.2%; p<0.05). In conclusion, although nebivolol reduces blood pressure and blood pressure variability in bothgroups, no significant differences were found in the pharmacokinetics and cardiovascular effects of fructose-fed rats, exceptfor lower bradycardic efficacy and greater reduction in short-term blood pressure variability.