The relationship of alprazolam and clonazepam dose to steady-state concentration in plasma.
This report addresses the correlation between dose and concentration of both alprazolam and clonazepam in plasma. Patients were 43 participants in a double-blind, placebo-controlled study of alprazolam and clonazepam for the treatment of panic disorder. The concentration of clonazepam in plasma was linearly related with dose, measured as milligrams per day (R = 0.724; F = 24.2; p = 0.0001) or milligrams per kilogram per day (R = 0.863; F = 58.3; p = 0.0001). The correlation between drug concentration and daily dose of alprazolam was also significant (R = 0.60; F = 9.5; p = 0.007), although the correlation between dose measured as milligrams per kilogram per day and drug level was not significant (R = 0.361; F = 2.4; p = 0.14). This replicates previous findings that, for each additional milligram per day dose of alprazolam, there is a corresponding increase of approximately 10 ng/ml in the plasma and presents preliminary data that, for each added 1 mg/day dose of clonazepam, there is approximately an increase of 12 ng/ml in the plasma. For both drugs, however, there may be considerable variation in level in plasma for a given dose. Weight-adjusted clonazepam concentration may be more predictable than weight-adjusted alprazolam concentration.
Labbate
L A
LA
Department of Psychiatry, Walter Reed Army Medical Center, Washington, D.C. 20307.
Pollack
M H
MH
Otto
M W
MW
Tesar
G M
GM
Rosenbaum
J F
JF
D000293:Adolescent; D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002998:Clonazepam / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D016584:Panic Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology
D002998:Clonazepam; D000525:Alprazolam