Pharmacokinetics of alprazolam in elderly patients with multiple diseases

The pharmacokinetics of alprazolam (1 mg p.o.) were investigated (using a new developed HPLC-assay) in 10 multimorbid elderly patients (five female, five male; mean age 72.8 +/- 8.2 years, creatinine clearance 63.6 +/- 25.9 ml/min, weight 68.9 +/- 13.9 kg). Compared with young and elderly volunteers from other studies peak plasma concentrations of alprazolam were decreased while peak time and elimination half-life were increased. 'Second peak' plasma levels (correlated with age and creatinine clearance) occurred in eight of 10 elderly patients. The variability associated with the pharmacokinetic parameters in the multimorbid elderly patients was far greater than that observed in young and old healthy volunteers. Mean alprazolam concentrations in multimorbid patients aged 72 years or more were elevated as compared to 'younger' patients (age range: 63-71 years). Dose reduction should be considered in the older multimorbid patients.