Relationship between patient variables and plasma clozapine concentrations: a dosing nomogram.
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.
Perry
P J
PJ
Department of Psychiatry, College of Medicine, University of Iowa, Iowa City 52242, USA.
Bever
K A
KA
Arndt
S
S
Combs
M D
MD
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D003024:Clozapine / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008960:Models, Psychological; D012044:Regression Analysis; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012727:Sex Characteristics; D012907:Smoking / Q000378:metabolism
D014150:Antipsychotic Agents; D003024:Clozapine