Effect of Age on Pharmacokinetics of and Blood Pressure Responses to Prazosin and Terazosin

Abstract

Prazosin and terazosin are two .alpha.1-adrenoceptor blocking agents, their principal difference being the longer half-life of terazosin. The present study was carried out to determine if elderly subjects are different from the young in their pharmacokinetic handling of these two drugs and if age influences the blood pressure response to each drug. Ten young healthy subjects (aged 19-30 years) and five older healthy subjects (aged 54-62 years) received 1 or 2 mg terazosin, 1 or 2 mg prazosin, or placebo 1 week apart according to a 5 .times. 5 Latin square design. Concentrations of prazosin and terazosin were measured using a high-performance liquid chromatographic procedure with a detection limit of .apprx. 0.25 ng/ml. Pharmacokinetic parameters of prazosin were virtually the same in both groups, whereas mean terazosin plasma concentrations were higher were higher in the older group and pharmacokinetic analysis revealed higher peak plasma concentrations and a longer terminal elimination half-life. There was no evidence of increased sensitivity to the hypotensive action of the drug, as peak upright blood pressure falls were similar in the two groups. Symptoms of dizziness in the upright position were also less common. In view of their lack of sedative effects and minimal metabolic disturbances, further studies should be conducted to assess the suitability of these drugs as monotherapy for hypertension in elderly patients.