Influence of Cyp2D6 genetic polymorphism on ratios of steady-state serum concentration to dose of the neuroleptic zuclopenthixol.
One hundred and nineteen psychiatric patients undergoing therapeutic drug monitoring (TDM) of the neuroleptic zuclopenthixol were genotyped with regard to Cyp2D6. Twelve patients (10.1%) were of the poor metabolizer genotype. The extensive metabolizers comprised 58 patients receiving no potentially interacting drugs and 38 patients concomitantly treated with other drugs competing for metabolism by Cyp2D6. Information on the rest (11 patients) was missing. The median steady-state serum concentration-to-dose ratio (C/D) of the PM group (2.00 nmol/L/mg) was close to that of the EM group receiving potentially interacting drugs (1.80) and approximately 60% higher than that of the remaining EM group (1.25) (p < 0.01). When judging the clinical importance of this difference, the total group variability in C/D of nearly 10-fold should be kept in mind (0.5-4.2 nmol/L/mg). In terms of serum concentrations not corrected for dose, the three groups had about similar levels, with median values from 16 to 21 nmol/L. We consider that TDM adequately takes into account dose adjustments for both EM and PM subjects in the context of this neuroleptic.
Linnet
K
K
Institute for Basic Research in Psychiatry, Psychiatric Hospital, Aarhus, Risskov, Denmark.
Wiborg
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D003006:Clopenthixol / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D003718:Denmark; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000201:enzymology; D008875:Middle Aged; D011110:Polymorphism, Genetic
D014150:Antipsychotic Agents; D003006:Clopenthixol; D019389:Cytochrome P-450 CYP2D6