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  • Title: Pharmacokinetics and clinical effects of alprazolam following single and multiple oral doses in patients with panic disorder.
    Author: Ciraulo DA, Barnhill JG, Boxenbaum HG, Greenblatt DJ, Smith RB.
    Journal: J Clin Pharmacol; 1986 Apr; 26(4):292-8. PubMed ID: 2871050.
    Abstract:
    The anxiolytic triazolobenzodiazepine alprazolam was administered to six male patients, aged 26 to 46 years, with panic disorder or agoraphobia (with panic attacks) to assess clinical effects and steady-state pharmacokinetics following multiple dosing at three levels: 3.0 mg/d, 6.0 mg/d, and 9.0 mg/d. Multiple-dose kinetics of alprazolam were compared with alprazolam disposition after a 1.0-mg oral dose in the same patients. Kinetic variables after the single dose were very similar to those reported previously for healthy young male volunteers. Mean values were peak plasma concentration, 19 ng/mL; time of peak, 1.33 hours after dosage; elimination half-life, 10.0 hours; total oral clearance, 1.11 mL/min/kg. During multiple dosage, mean steady-state plasma concentrations (Css) was proportional to dosing rate, and steady-state clearance was independent of dosage. Clinical improvement was rapid, with the greatest decrement in symptoms at the 3-mg/d dosage, at a mean Css of 30 ng/mL. Further improvement was not seen at 6 mg/d (Css, 62 ng/mL), or at 9 mg/d (Css, 103 ng/mL). Side effects, however, were directly related to dosage and plasma level, and increased progressively in number at the 3-, 6-, and 9-mg/d dosage levels. Thus, the disposition of alprazolam in young male patients with panic disorder is essentially identical to that in healthy male volunteers of similar age. Alprazolam clearance is independent of dose and plasma concentration up to daily doses of at least 9 mg/d, with steady-state plasma level proportional to dosing rate.
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