F224. UTILITY OF SALIVA FOR MONITORING OF CLOZAPINE LEVELS
Bibliographic record
Abstract
Clozapine has specific indication for use in Treatment Resistant Schizophrenia (TRS) with guidelines for therapeutic drug monitoring. Though a plasma level > 350 ng/ml has been cited as the therapeutic threshold, many other studies have shown poor or inconsistent associations between blood levels of clozapine and side effects. Clozapine is about 95% bound to plasma proteins with a small biologically active fraction. Saliva presents as a promising alternative for therapeutic drug monitoring where clozapine levels would be at equilibrium with free unbound clozapine in the plasma. This provides the added advantage of a potentially stronger relationship with efficacy and adverse effects when compared to plasma levels because of saliva’s closer representation of biologically-active clozapine. Salivary collection is also non-invasive and can be sampled serially for more precise evaluation of intra-individual variations. In the present investigation, we set out to evaluate the agreement and comparative clinical utility between plasma and salivary clozapine levels. 53 participants with schizophrenia and on stable doses of clozapine for at least 2 weeks were recruited for the study. Participants had to undergo a clinical interview and the SCID, PANSS, plus side effect scales were administered. Symptomatic remission status was defined using the symptom criteria proposed by Andreasen et al (2005). A fasting sample of venous blood and salivary sample were collected at the same time. Assays for clozapine and norclozapine were performed using high performance liquid chromatography. A total of 106 saliva and plasma samples have been analysed. Our results showed strong correlations between plasma and salivary levels of clozapine (r=0.61, P<0.05) and norclozapine (r=0.63, P<0.05). Twenty (37.7%) participants achieved symptomatic remission at the time of recruitment. Non-remitters had a significantly higher level of plasma clozapine. Thirty-one (93.9%) participants in the non-remitter group have plasma clozapine levels greater than 350ng/ml. Our study shows potential for salivary samples to be an alternate non-invasive source for therapeutic drug monitoring of clozapine. This will be useful in serial monitoring of clozapine levels to evaluate treatment adherence and fluctuating pharmacokinetic profiles. There is a significant proportion of patients who do not achieve symptomatic remission on clozapine, which highlights a pressing need to identify new pharmacological agents or modalities of treatment.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".