Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition
Copyright © 2023 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Schizophrenia research - (2023) vom: 31. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schoretsanitis, Georgios [VerfasserIn] |
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| Links: |
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| Themen: |
Asian continental ancestry group |
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| Anmerkungen: |
Date Revised 02.06.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.schres.2023.05.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357704878 |
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| 245 | 1 | 0 | |a Clozapine ultrarapid metabolism during weak induction probably exists but requires careful diagnosis. A literature review, five new cases and a proposed definition |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a CYP1A2 | |
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| 700 | 1 | |a Anıl Yağcıoğlu, A Elif |e verfasserin |4 aut | |
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| 700 | 1 | |a Eap, Chin B |e verfasserin |4 aut | |
| 700 | 1 | |a Molden, Espen |e verfasserin |4 aut | |
| 700 | 1 | |a Baptista, Trino |e verfasserin |4 aut | |
| 700 | 1 | |a Clark, Scott R |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez-Egea, Emilio |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Se Hyun |e verfasserin |4 aut | |
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| 700 | 1 | |a Procyshyn, Ric M |e verfasserin |4 aut | |
| 700 | 1 | |a Rohde, Christopher |e verfasserin |4 aut | |
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