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.