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ANTIPSYCHOTIC THERAPEUTIC DRUG MONITORING: EVALUATION OF THE ROLE OF ORAL FLUID, AND PLASMA QUETIAPINE METABOLITE ASSAYS

Student thesis: Doctoral ThesisDoctor of Philosophy

Therapeutic drug monitoring (TDM) is the measurement of drugs and/or metabolites in biological samples to guide therapy. TDM for antipsychotic drug therapy in schizophrenia treatment is well-established if adherence is in doubt and in dose optimisation.

The antipsychotic quetiapine has a short plasma half-life and no clear reference range for clinical response. Three quetiapine metabolites, N-desalkylquetiapine, O-desalkylquetiapine and 7-hydroxyquetiapine, were investigated in routine plasma TDM samples to determine whether they provide useful information to assess quetiapine exposure. Compared to median plasma quetiapine concentrations, N-desalkylquetiapine, O-desalkylquetiapine and 7-hydroxyquetiapine plasma concentrations were equivalent, 1/10th and 1/20th, respectively. All metabolites showed greater correlation to dose than quetiapine itself; dose-related plasma concentrations have been presented to aid future results interpretation.

Blood sampling is invasive; hence, oral fluid was investigated as an alternative matrix. A clinical study was undertaken to investigate the relationship between analyte concentrations in oral fluid samples collected using different oral fluid collection devices [Greiner Bio-One (GBO; in-mouth buffered collected system), and Thermo Oral-Eze] and in plasma. Existing plasma LC-M/MS methods were combined, and sample preparation modified to be suitable for acidified (buffered) oral fluid samples. The methods were assessed to ensure they were fit-for-purpose.

Relationships between plasma and oral fluid concentrations of clozapine and norclozapine were poor, and no better than results obtained using unstimulated oral fluid collected via the drool method. Median concentrations of all analytes were lower in the GBO samples than Oral-Eze samples; however, clozapine and norclozapine concentrations in samples collected using the proprietary devices were approximately twice the concentration measured in samples collected by the drool method, as a ratio to plasma concentrations. Concentration differences are possibly related to differing salivary stimulation during sample collection. A positive finding was a patient who had become non-adherent to clozapine was identified from oral fluid as well as plasma analysis.
Original languageEnglish
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Award date2017

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