Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
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Plasma Concentrations of Clozapine and its Metabolites and FMO3 Variations in Korean Schizophrenic Patients

정신분열병 환자에서 Clozapine과 그 대사물들의 혈장농도 및 FMO3 유전자 변이

  • Lee, Kyung-Hoon (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine/Clinical Trial Center, Clinical Research Institute, Samsung Medical Center) ;
  • Kim, Chul Eung (Department of Psychiatry, College of Medicine, Inha University, Inha University Hospital)
  • 이경훈 (성균관대학교 의과대학 분자세포생물학교실/삼성서울병원 임상의학연구소 임상시험센터) ;
  • 김철응 (인하대학교 의과대학 인하대병원 정신과학교실)
  • Published : 2006.08.31
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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.

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