THE RELATIONSHIP OF ALPRAZOLAM DOSE TO STEADY-STATE PLASMA-CONCENTRATIONS

Alprazolam is a widely used antianxiety agent,yet relatively little ia known about the relationship between chronic oral doses and steady-state plasma leves. this study examins the relationship over a wide range of therpeutic doses. We conducted a parallel, double-blind, placebo-controlled study in 36 patients with agoraphobia with panic attacks,or panic diaorder with limited phobic avoidance base4d on DSM-III criteria. Patients received alprazolam(N=25)or placebo(N=11)begining at 1 mg/day and increased weekly until either a maximum tolearted dose or 10mg/day was achieved. Dosages were then gradually tapered according to a predetermine schedule. The entire study period lasted 14 weeks. Laboratory and clinical assessments were conducted weekly. Dose up to 6 mg/day were tolearted by 10 mg/day were tolerated by 40% of patients. Twenty-seven percent of the palacebo patients reached10 tablets/day. In the alprazolam group,the principal cause of intolerance was sedation.Throughout the study no significant change in vital sign or laboratory parameter were observed. Steady state alprazolam, 4-hydroxy alprazolam,and a-hydroxy alprazolam plasma levels were linearly related to dose. A 1 mg dosage increment produced, on the average, a corresponding 10 ng/ml increase in steady state level of the parent drug.Significant response was observed in subject who nificant response was observed in subject who achieved concentrations graeter than 20 ng/ml, with a maximum of 81% of the samles classified as responders whithin the 60 ng/ml and above group. During taper, no severe withdrawal symptoms were noted; 12 of 25 alprazolam patients, however, reported rebond anxiety(anxiety rating scale scores higher than baseline),which occurred most commonly at the reduction from 1 mg to 0 mg. © 1990 Williams and Wilkins.