The effect of aging on the pharmacokinetics and pharmacodynamics of prazosin

Abstract.

Objective: The effect of age on the pharmacokinetics and pharmacodynamics of prazosin (α₁ adrenoceptor blocker) was studied in 20 healthy volunteers.

Patients:

Ten elderly (61–81 y) and ten young (23–28 y) subjects were studied. All subjects received 1 mg of prazosin orally in a fasting state. Serial blood samples were collected for calculation of oral pharmacokinetics, and blood pressure and pulse rate were measured during blood collection. Subjects remained supine and fasting for the first three hours post drug administration, after which they were allowed to ambulate and eat.

Results:

The oral pharmacokinetics of prazosin were not different in the two age groups. The serum t_1/2 in the elderly was 210 min while in the young group was 139 min. The AUC_0−∞ in the two groups was not different. The C_max was identical in the two groups, and the time to C_max was 84 min in the elderly and 114 min in the young subjects. Protein binding was 93.4% in the elderly and 93.5% in the young subjects and the serum α₁ acid glycoprotein concentration was not different in the two groups of subjects.

Even though the pharmacokinetics of prazosin were unchanged by age, the haemodynamic effects of the drug were greater in the elderly. The fall in systolic blood pressure and mean blood pressure was significantly greater in the elderly group at multiple time points after drug administration while the change in diastolic blood pressure was equivalent in the two age groups. Despite a greater decrease in mean blood pressure in the elderly, the compensatory increase in heart rate was similar in the two age groups suggesting a difference in the baroreceptor reflex in the two age groups.

Conclusion:

The results of this study demonstrate that age does not alter the pharmacokinetics of oral prazosin, but the pharmacodynamic response at equivalent plasma prazosin concentration is greater in the elderly.