dc.date.accessioned | 2022-10-28T15:41:16Z | |
dc.date.available | 2022-10-28T15:41:16Z | |
dc.date.created | 2022-10-14T09:37:59Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Kyllesø, Lennart Smith, Robert Løvsletten Wollmann, Birgit Malene Tovik Karlstad, Øystein Andreassen, Ole Molden, Espen . Metabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment: A Retrospective Pilot Study. Journal of Clinical Psychopharmacology. 2022, 42(5), 470-474 | |
dc.identifier.uri | http://hdl.handle.net/10852/97402 | |
dc.description.abstract | Purpose/Background
Pharmacokinetics may be of relevance for the risk of clozapine discontinuation. We compared metabolite profiles, accounting for smoking habits, in patients switching versus maintaining clozapine treatment at therapeutic concentrations.
Methods/Procedures
Adult patients with clozapine serum levels above 1070 nmol/L (350 ng/mL) were retrospectively included from a Norwegian therapeutic drug monitoring service during 2018–2020. Inclusion criteria were (1) known smoking habits, (2) blood sample drawn within 10 to 30 hours after last clozapine intake, and (3) detectable levels of N-desmethylclozapine, clozapine-N-oxide, clozapine-5N-glucuronide, or clozapine-N+-glucuronide. Patients comedicated with cytochrome P450 enzyme inducers, inhibitors, or valproic acid were excluded. The high-resolution mass spectrometry assay enabled detection of 21 clozapine metabolites. Metabolite profiles were compared between patients switching treatment (switchers), measured as clozapine being replaced by another antipsychotic drug in blood samples, versus maintaining clozapine treatment (nonswitchers) during the study period.
Findings/Results
Of the 84 patients fulfilling the study criteria, 7 patients (8.3%) were identified as clozapine switchers. After correcting for smoking habits, the clozapine-5N-glucuronide/clozapine ratio was 69% lower (P < 0.001), while the clozapine-N+-glucuronide/clozapine-5N-glucuronide ratio was 143% higher (P = 0.026), respectively, in switchers versus nonswitchers. The other metabolite ratios did not significantly differ between switchers and nonswitchers.
Implications/Conclusions
The present study found a significantly reduced 5N-glucuronidation phenotype in patients switching from clozapine at therapeutic serum concentrations (>1070 nmol/L) to other antipsychotic drugs. This may indicate that glucuronidation, as a potential detoxification mechanism, is related to clozapine tolerability. However, the causality of this observation needs to be investigated in future studies with larger patient populations. | |
dc.language | EN | |
dc.publisher | Lippincott Williams & Wilkins | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.title | Metabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment: A Retrospective Pilot Study | |
dc.title.alternative | ENEngelskEnglishMetabolite Profiling of Clozapine in Patients Switching Versus Maintaining Treatment: A Retrospective Pilot Study | |
dc.type | Journal article | |
dc.creator.author | Kyllesø, Lennart | |
dc.creator.author | Smith, Robert Løvsletten | |
dc.creator.author | Wollmann, Birgit Malene Tovik | |
dc.creator.author | Karlstad, Øystein | |
dc.creator.author | Andreassen, Ole | |
dc.creator.author | Molden, Espen | |
cristin.unitcode | 185,53,10,70 | |
cristin.unitname | NORMENT part UiO | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 2061378 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal of Clinical Psychopharmacology&rft.volume=42&rft.spage=470&rft.date=2022 | |
dc.identifier.jtitle | Journal of Clinical Psychopharmacology | |
dc.identifier.volume | 42 | |
dc.identifier.issue | 5 | |
dc.identifier.startpage | 470 | |
dc.identifier.endpage | 474 | |
dc.identifier.doi | https://doi.org/10.1097/JCP.0000000000001585 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0271-0749 | |
dc.type.version | PublishedVersion | |