RELATIONSHIP BETWEEN PATIENT VARIABLES AND PLASMA CLOZAPINE CONCENTRATIONS - A DOSING NOMOGRAM

Background: Previous work has suggested factors such as gender, smokin g behavior, dose, and age affect the amount of drug a patient requires to achieve a desired plasma concentration of clozapine. Plasma clozap ine concentrations ranging from 350 to 504 ng/mL in treatment-refracto ry schizophrenics and schizoaffective patients produce response rates ranging approximately 55-80%. Without the aid of clozapine plasma conc entration monitoring, 3-6 months are recommended for a therapeutic clo zapine trial. Data suggest that the lag time to response can be reduce d by administering a dose that produces a therapeutic clozapine concen tration. Methods: To generate a clozapine dosing nomogram to predict c lozapine steady-state plasma concentrations, a cohort of 71 patients w as 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 indep endent variables. Results: The dosing model that optimally predicted s teady-state clozapine plasma concentrations included the variables dos e (mg/day), smoking (yes = 0 and no = 1), gender, and a dose-gender in teraction variable. The model explained 47% of the variance in the clo zapine concentrations (F = 14.42, p <.001, r(2) = .47). Two equations, one for male subjects, i.e,, clozapine (ng/mL) 111 (smoke) + 0.464 (d ose) + 145, and one for female subjects, i.e., clozapine (ng/mL) = 111 (smoke) + 1.590 (dose) - 149, were derived to predict clozapine stead y-state plasma concentrations to serve as a clozapine dosing guide for clinicians.Conclusions: A clozapine dosing nomogram was constructed a s a clinical aid to facilitate clozapine dosing. Biol Psychiatry 1998; 44:733-738 (C) 1998 Society of Biological Psychiatry.