240. SALIVA VERSUS PLASMA THERAPEUTIC DRUG MONITORING OF CLOZAPINE AND NORCLOZAPINE

Abstract Background Therapeutic drug monitoring (TDM) of clozapine is presently done via a blood sample collection. However, it is challenging to obtain a sample within the appropriate 12 hours post dose time window. Consequently, this impacts clinical interpretation in clozapine TDM. Saliva is a non-invasive and convenient sample source for TDM and has been used in monitoring of carbamazepine and lithium levels. Clozapine is highly protein bound in plasma, but saliva has the additional benefit of containing only free fraction of clozapine, which might provide a stronger association with clozapine side effects. Aims & Objectives This study aimed to (1) examine correlations between plasma and saliva clozapine and norclozapine, (2) compare predictors of blood and saliva clozapine levels, and (3) investigate associations between common clozapine side effects and clozapine levels obtained from blood and saliva. Method Blood and saliva samples were collected in a single visit from 155 patients on clozapine. Clozapine and norclozapine levels were assayed using high-performance liquid chromatography with ultraviolet/visible detection (HPLC-UV). CYP1A2 metabolising status and known non-genetic factors, i.e. sex, smoking status, caffeine intake and antidepressant use, influencing clozapine plasma levels were assessed. Common clozapine side effects, including hypersalivation, sedation, constipation and QTc prolongation were assessed. Results The median daily clozapine dose was 300 mg/day. The median plasma clozapine concentration and concentration-to-dose (CD) ratio were 749 ng/ml and 2.6 ng/ml per mg/day, respectively. Clozapine was detected in 151 (97.4%) saliva samples. The median clozapine levels and CD ratio in saliva were 210 ng/ml and 0.8 ng/ml per mg/day. Significant correlations were observed between plasma and saliva levels of clozapine (rs = 0.577, p < 0.001) and norclozapine (rs = 0.491, p < 0.001). In the multivariate model, CYP1A2 induction status, antidepressant use and sampling time were significantly associated with plasma clozapine levels. In saliva, CYP1A2 induction status was the sole factor associated with clozapine levels. Of the four clozapine side effects assessed, only QTc prolongation was significantly associated with both plasma and saliva clozapine concentrations. Discussion & Conclusions Our study provides insights into the predictors of clozapine levels and supports the use of saliva for monitoring of clozapine levels and patient adherence. In addition, our findings underscore the importance of CYP1A2 induction status and antidepressant use as key influencers of clozapine levels, contributing to more informed prescribing practices. Further research is warranted to confirm and expand upon these findings.