Single‐Dose Pharmacokinetics and Pharmacodynamics of Alprazolam in Elderly and Young Subjects

Abstract

The pharmacokinetics and pharmacodynamics of the benzodiazepine anxiolytic alprazolam (1 mg orally) were compared between young and elderly healthy volunteers. Eight young subjects (mean age 29.8 years) and eight elderly volunteers (mean age 68.4 years) received oral placebo and alprazolam (1.0 mg) in a randomized, double-blind, single-dose crossover study. In the elderly subjects, plasma concentrations were higher, although not significantly so, than in young volunteers 0.25, 0.5, and 0.75 hours after dosage. Apparent elimination half-life, time of maximum concentration, maximum concentration, volume of distribution, and apparent clearance were similar for the two groups. In both groups, alprazolam treatment (versus placebo) produced significant changes in typical benzodiazepine agonist effects, such as increased sedation and fatigue, reduced excitement, increased feelings of spaciness, and perception of thinking slowed. For some measures, the alprazolam-placebo difference was greater in young than in elderly subjects. In both groups, alprazolam significantly impaired performance on the digit-symbol substitution test (DSST). EEG studies indicated significant increases in relative beta amplitude (13-30 Hz range) after alprazolam compared to placebo. Percent DSST decrement and percent EEG change were highly correlated with plasma alprazolam concentrations for both groups. There were modest increases in alprazolam plasma concentration in the elderly compared to the younger group shortly after drug administration, but there was no evidence of increased sensitivity to the pharmacodynamic effects of alprazolam in the elderly.

Increased sensitivity to alprazolam in females with a paternal history of alcoholism

“…Given that alprazolam metabolism has not been shown to vary across the menstrual cycle (Kirkwood et al 1991), andCiraulo et al (1996) reported that alprazolam plasma levels were similar in FHP and FHN females following a single dose of alprazolam, we did not feel that collecting plasma levels in the present study was justified. However, changes in both electrophysiological activity and DSST performance have been shown to be correlated with alprazolam plasma levels (Kaplan et al 1998). Further, in a recent study (SaridSegal et al 2000), alprazolam plasma levels tended to be higher in FHP individuals than FHN individuals.…”

Alprazolam Attenuates the Behavioral Effects of d-Amphetamine in Humans

“…46 Peak alprazolam plasma concentrations occur approximately 2 hours after oral administration. [47][48][49][50] Based on these pharmacokinetic data, D-amphetamine and alprazolam were administered simultaneously to assess behavioral effects across peak plasma levels of both drugs.…”

Symbol–digit substitution and individual differences in visual search ability

“…Performance on the test was a significant variable in discriminant function analyses of long-and short-term schizophrenics (Royer & Janowitch, 1973). Substitution tests also have utility in demonstrating the effects of alcohol and medications on performance (e.g., Cameron, Sinclair, & Tiplady, 2001;Kaplan et al, 1998;Mattila, Aranko, Mattila, & Paakkari, 1994). Despite the wide application of substitution tests there is no clear agreement on what the test measures.…”