A B S T R A C T

Safe and effective administration of clozapine requires careful monitoring for inflammatory reactions during the

initial titration. The concentration-to-dose (C/D) ratio must be taken into account, which may vary among

ethnicities. In this retrospective study, 1408 Korean schizophrenia inpatients were examined for during the first

8 weeks of clozapine titration. The average doses of clozapine administered during weeks 1, 2, 4, and 8 were

77.37, 137.73, 193.20, and 212.83 mg/day, with significantly lower doses for females than males. The average

C/D ratio was significantly higher in females (1.75 ± 1.04 and 1.11 ± 0.67 ng/mL per mg/day). Patients with

higher C/D ratios were more likely to experience fever and were prescribed lower doses of clozapine starting

from week 4. In total, 22.1 % of patients developed a fever at an average of 15.74 days after initiating clozapine.

Patients who developed a fever were younger, used more antipsychotics at baseline, had a higher C/D ratio, and

had a higher incidence of an elevated C-reactive protein level. A higher C/D ratio, use of a greater number of

antipsychotics at baseline, and concomitant olanzapine use were risk factors for the development of inflammatory

reactions. The incidence of pneumonia, agranulocytosis, and myocarditis within 8 weeks were 3.7 %, 0.3

%, and 0.1 %. In summary, the target dose of clozapine titration is lower for Korean schizophrenia patients, with

a higher C/D ratio and more frequent fever compared to Western patients; however, myocarditis occurs rarely.

Our findings may contribute to the titration methods for clozapine for the East Asian population.