Oct, 1, 2023

Vol.30 No.2, pp. 84-88

Current Issue Archives
Search
Advanced Search
Editorial Office

Review

  • Korean Journal of Biological Psychiatry
  • Volume 13(3); 2006
  • Article

Review

Korean Journal of Biological Psychiatry 2006;13(3):152-61. Published online: Mar, 1, 2006

Abstract PDF Full Text

Plasma Concentrations of Clozapine and its Metabolites and FMO3 Variations in Korean Schizophrenic Patients

  • Kyung-Hoon Lee, MD, PhD1; and Chul Eung Kim, MD, PhD2;
    1;Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine/Clinical Trial Center, Clinical Re-search Institute, Samsung Medical Center, Seoul, 2;Department of Psychiatry, College of Medicine, Inha University, Inha University Hospital, Incheon, Korea
Abstract

Objective：The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type：Glu, 'H'；variant：Lys, 'h') and Glu308Gly(wild-type：Glu, 'D'；variant：Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients.

　

Methods：Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. 

　

Results：A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles.

　

Conclusion：The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.

Keywords Clozapine;Clozapine <i>N</i>-oxide;Flavin-containing monooxygenase 3(<i>FMO3</i>);Genetic variation;Schizophrenia.