Correlation Between Clozapine and CRP Levels in Relation to Smoking Status

Both inflammation and smoking are known to affect clozapine metabolism. However, the impact of inflammation on clozapine metabolism in relation to smoking status is unclear. Therefore, we investigated correlations between C-reactive protein (CRP) and clozapine levels in smokers and non-smokers separately.

Patients were included retrospectively from a therapeutic drug monitoring (TDM) service in Oslo, Norway, during January 2005-April 2022. Inclusion criteria were known smoking status and CRP measurements no longer than 7 days before or after clozapine TDM. Exclusion criteria were confirmed blood sampling for TDM outside 10-30 h after the last clozapine intake. Information about clozapine dosing was retrieved from the requisition forms.

In 126 patients fulfilling the criteria (47% smokers), dose-adjusted serum concentration (CD) of clozapine correlated significantly with CRP in non-smokers (R = 0.492; p < 001) but not in smokers (R = 0.191; p = 0.166). When subgrouping non-smoking patients into low CRP (< 5 mg/L; reference [51% of the population]), mid CRP (5-50 [37%]) and high CRP (> 50 [12%]), clozapine CD gradually increased in mid- (+48%, p = 0.004) and high-CRP groups (+204%, p < 0.001) compared with the low-CRP group. No significant differences in clozapine CD were found between CRP groups among smokers (p > 0.15).

We report a significant correlation between CD of clozapine and CRP levels in non-smoking patients only. In these patients, clozapine CD is more than 3-fold higher at CRP > 50 versus CRP < 5. This suggests that non-smokers are most susceptible to clozapine side effects during inflammation or infection and represent patients where TDM analyses are especially important for guiding clozapine dosing.