ALPRAZOLAM ABSORPTION KINETICS AFFECTS ABUSE LIABILITY

Objective: To evaluate the behavioral, subjective, and reinforcing eff ects of immediate-release (IR) alprazolam and extended-release (XR) al prazolam to assess the effect of release rate on laboratory measures o f abuse liability. Methods: Fourteen healthy men with histories of sed ative abuse participated as subjects in a double-blind crossover study . All subjects received placebo, 1 and 2 mg immediate-release alprazol am, and 2 and 3 mg extended-release alprazolam in random order. Behavi oral performance, subjective effects, and alprazolam plasma concentrat ions were assessed repeatedly 1/2 hour before and 1/2, 1, 3, 5, 7, 9, 12, and 24 hours after drug administration. Results: Mean peak alprazo lam plasma concentrations occurred 1.7 and 9.2 hours after immediate-r elease alprazolam and extended-release alprazolam, respectively. Compa red to placebo, 2 mg immediate-release alprazolam impaired all measure s of psychomotor and cognitive performance (Digit Symbol Substitution Test), motor coordination (circular lights and balance), and memory (d igit entry and recall); 2 mg extended-release alprazolam did not aged any of these measures and 3 mg extended-release alprazolam impaired ci rcular lights only. Immediate-release alprazolam, 2 mg, increased all six measures of positive drug effects (e.g., ratings of liking or good effects); none of these measures were increased by 2 mg extended-rele ase alprazolam and only three of the six measures were increased by 3 mg extended-release alprazolam. A drug versus money multiple-choice pr ocedure designed to assess the relative reinforcing effects of each co ndition was administered 24 hour after the drug. The amount of money s ubjects were willing to ''pay'' to take the drug was significantly gre ater than placebo for both doses of immediate-release alprazolam but f or neither dose of extended-release alprazolam. Conclusions: These dat a indicate that extended-release alprazolam has less potential for abu se than immediate-release alprazolam.