Linnet K, Wiborg O
Institute for Basic Research in Psychiatry, Psychiatric Hospital, Aarhus, Risskov, Denmark.
Ther Drug Monit. 1996 Dec;18(6):629-34. doi: 10.1097/00007691-199612000-00001.
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.
对119例接受抗精神病药物珠氯噻醇治疗药物监测（TDM）的精神病患者进行了细胞色素P450 2D6（Cyp2D6）基因分型。12例患者（10.1%）为代谢不良基因型。广泛代谢者包括58例未服用可能存在相互作用药物的患者以及38例同时接受其他与Cyp2D6代谢竞争药物治疗的患者。其余11例患者的信息缺失。代谢不良组的稳态血清浓度与剂量比（C/D）中位数（2.00 nmol/L/mg）与接受可能存在相互作用药物的广泛代谢组（1.80）相近，比其余广泛代谢组（1.25）高约60%（p<0.01）。在判断这种差异的临床重要性时，应牢记C/D的总体组内变异性近10倍（0.5 - 4.2 nmol/L/mg）。就未校正剂量的血清浓度而言，三组水平大致相似，中位数为16至21 nmol/L。我们认为，在这种抗精神病药物的情况下，治疗药物监测充分考虑了广泛代谢者和代谢不良者的剂量调整。
