Relationship between patient variables and plasma clozapine concentrations: a dosing nomogram

Abstract

Background: Previous work has suggested factors such as gender, smoking behavior, dose, and age affect the amount of drug a patient requires to achieve a desired plasma concentration of clozapine. Plasma clozapine concentrations ranging from 350 to 504 ng/mL in treatment-refractory schizophrenics and schizoaffective patients produce response rates ranging approximately 55-80%. Without the aid of clozapine plasma concentration monitoring, 3-6 months are recommended for a therapeutic clozapine trial. Data suggest that the lag time to response can be reduced by administering a dose that produces a therapeutic clozapine concentration.

Methods: To generate a clozapine dosing nomogram to predict clozapine steady-state plasma concentrations, a cohort of 71 patients was collected via retrospective chart review and/or patient interview. Clozapine steady-state plasma concentrations and demographic variables were obtained. Multiple-linear regression was utilized to examine the relationship between the plasma clozapine concentration and the independent variables.

Results: The dosing model that optimally predicted steady-state clozapine plasma concentrations included the variables dose (mg/day), smoking (yes = 0 and no = 1), gender, and a dose-gender interaction variable. The model explained 47% of the variance in the clozapine concentrations (F = 14.42, p < .001, r2 = .47). Two equations, one for male subjects, i.e., clozapine (ng/mL) = 111 (smoke) + 0.464 (dose) + 145, and one for female subjects, i.e., clozapine (ng/mL) = 111 (smoke) + 1.590 (dose)-149, were derived to predict clozapine steady-state plasma concentrations to serve as a clozapine dosing guide for clinicians.

Conclusions: A clozapine dosing nomogram was constructed as a clinical aid to facilitate clozapine dosing.