Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition.

Details

Serval ID
serval:BIB_3AF533499666
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition.
Journal
Schizophrenia research
Author(s)
Schoretsanitis G., Anıl Yağcıoğlu A.E., Ruan C.J., Eap C.B., Molden E., Baptista T., Clark S.R., Fernandez-Egea E., Kim S.H., Lane H.Y., Leung J., Maroñas Amigo O., Motuca M., Olmos I., Every-Palmer S., Procyshyn R.M., Rohde C., Satish S., Schulte PFJ, Spina E., Takeuchi H., Verdoux H., Correll C.U., de Leon J.
ISSN
1573-2509 (Electronic)
ISSN-L
0920-9964
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
During weak induction (from smoking and/or valproate co-prescription), clozapine ultrarapid metabolizers (UMs) need very high daily doses to reach the minimum therapeutic concentration of 350 ng/ml in plasma; clozapine UMs need clozapine doses higher than: 1) 900 mg/day in patients of European/African ancestry, or 2) 600 mg/day in those of Asian ancestry. Published clozapine UMs include 10 males of European/African ancestry, mainly assessed with single concentrations. Five new clozapine UMs (two of European and three of Asian ancestry) with repeated assessments are described. A US double-blind randomized trial included a 32-year-old male smoking two packages/day with a minimum therapeutic dose of 1,591 mg/day from a single TDM during open treatment of 900 mg/day. In a Turkish inpatient study, a 30-year-old male smoker was a possible clozapine UM needing a minimum therapeutic dose of 1,029 mg/day estimated from two trough steady-state concentrations on 600 mg/day. In a Chinese study, three possible clozapine UMs (all male smokers) were identified. The clozapine minimum therapeutic dose estimated with trough steady-state concentrations >150 ng/ml was: 1) 625 mg/day, based on a mean of 20 concentrations in Case 3; 2) 673 mg/day, based on a mean of 4 concentrations in Case 4; and 3) 648 mg/day, based on a mean of 11 concentrations in Case 5. Based on these limited studies, clozapine UMs during weak induction may account for 1-2% of clozapine-treated patients of European ancestry and <1% of those of Asian ancestry. A clozapine-to-norclozapine ratio <0.5 should not be used to identify clozapine UMs.
Keywords
Asian continental ancestry group, Cyp1a2, Clozapine/blood, Clozapine/metabolism, Clozapine/therapeutic use, Smoking, CYP1A2
Pubmed
Create date
08/06/2023 14:32
Last modification date
13/12/2023 8:12
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