Alprazolam kinetics in the elderly. Relation to antipyrine disposition

Abstract

The pharmacokinetics of alprazolam, a triazolobenzodiazepine anxiolytic-antidepressant, were assessed in 32 healthy men and women aged 21 to 78 years after a single 1.0-mg oral dose. Peak alprazolam levels averaged 20.4 ng/mL and were reached a mean of 1.25 hours after dosage. Mean elimination half-life did not differ significantly between elderly and young women, nor did total metabolic clearance. However, half-life was significantly prolonged, and total clearance significantly reduced, in elderly v young men. Antipyrine oxidizing capacity was also evaluated, and half-life for the two drugs was highly correlated, as were their metabolic clearances. Thus, old age is associated with impaired capacity to oxidize alprazolam, but this effect is far more apparent in men than in women. A test of antipyrine half-life and clearance may help identify slow or rapid metabolizers of alprazolam.