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

Schoretsanitis G., ANIL YAĞCIOĞLU A. E., Ruan C., Eap C. B., Molden E., Baptista T., ...Daha Fazla

Schizophrenia Research, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.schres.2023.05.010
  • Dergi Adı: Schizophrenia Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus, Academic Search Premier, PASCAL, BIOSIS, CINAHL, Educational research abstracts (ERA), EMBASE, MEDLINE, Psycinfo, Public Affairs Index
  • Anahtar Kelimeler: Asian continental ancestry group, Clozapine/blood, Clozapine/metabolism, Clozapine/therapeutic use, CYP1A2, Smoking
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.