Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism.
Steady-state serum concentration to dose ratios of the neuroleptic agent perphenazine were related to CYP2D6 metabolizer status for 96 psychiatric inpatients: 88 extensive metabolizers and eight poor metabolizers. The median concentration per dose of the poor metabolizer group (0.195 nmol/L per milligram) was about twice the median (0.098 nmol/L per milligram) of the 56 extensive metabolizers without interacting medicine (p < 0.01). The rest of the extensive metabolizers (n = 32), who were comedicated with drugs that compete with perphenazine for metabolism by CYP2D6, had an intermediate median value of 0.140 nmol/L per milligram. The range of concentration/dose values for the total extensive metabolizer group extended from 0.025 to 0.688 nmol/L per milligram, that is, an almost thirtyfold variation. The concentration/dose range of the eight poor metabolizer subjects was 0.096 to 0.750 nmol/L per milligram. Serum levels not corrected for dose overlapped to a large degree among the groups, with a total range from 0.5 to 12 nmol/L. This study points toward a limited information value of CYP2D6 genotyping in the context of therapeutic drug monitoring of perphenazine.
Linnet
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K
Laboratory of Clinical Biochemistry, Psychiatric University Hospital of Aarhus, Risskov, Denmark.
Wiborg
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood*; D001483:Base Sequence; D002648:Child; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D010546:Perphenazine / Q000097:blood*; D011110:Polymorphism, Genetic
D014150:Antipsychotic Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D010546:Perphenazine