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Ther Drug Monit. 2012 Aug;34(4):415-21. doi: 10.1097/FTD.0b013e3182603f62.

Plasma concentrations of quetiapine, N-desalkylquetiapine, o-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide in relation to quetiapine dose, formulation, and other factors.

Author information

1
Toxicology Unit, Department of Clinical Biochemistry, Bessemer Wing, King's College Hospital NHS Foundation Trust, London, United Kingdom. danielle.fisher@nhs.net

Abstract

BACKGROUND:

N-Desalkylquetiapine may be a pharmacologically active quetiapine metabolite. However, information on plasma concentrations of N-desalkylquetiapine and other quetiapine metabolites attained during quetiapine therapy is scant. The aim of this study was to investigate plasma concentrations of quetiapine, N-desalkylquetiapine, O-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide attained during therapy and analyze the data with respect to prescribed dose and other variables.

METHOD:

Quetiapine and its metabolites were measured in plasma samples submitted for quetiapine therapeutic drug monitoring (2009-2011). Concentration, metabolic ratio, and concentration corrected for dose (C/D) were investigated against quetiapine dose, age, sex, and formulation. Sample results were excluded if nonadherence with therapy was queried.

RESULTS:

There were 99 samples from 59 patients. N-Desalkylquetiapine plasma concentrations showed the strongest correlation with dose of all analytes, but O-desalkylquetiapine and quetiapine sulfoxide were strongly correlated to plasma quetiapine concentrations. There was no significant difference in C/D for any analyte between males and females and no correlation to age. Quetiapine and quetiapine sulfoxide C/D were significantly different (P < 0.01) between patients prescribed immediate- and extended-release formulations. Quetiapine, 7-hydroxyquetiapine and quetiapine sulfoxide C/D showed significant variation (P < 0.02) between those samples taken 10-14 hours postdose as compared with that of 16-24 hours postdose, but there was no significant effect as regards N-desalkylquetiapine.

CONCLUSIONS:

Plasma quetiapine, O-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide concentrations were significantly affected by formulation and/or time since last dose. Plasma N-desalkylquetiapine concentrations were not affected by either factor therefore may be a better marker for quetiapine exposure than plasma quetiapine concentrations.

PMID:
22777152
DOI:
10.1097/FTD.0b013e3182603f62
[Indexed for MEDLINE]
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