Mannheimer Buster, Haslemo Tore, Lindh Jonatan D, Eliasson Erik, Molden Espen
*Karolinska Institutet, Department of Clinical Science and Education at Södersjukhuset, Stockholm, Sweden; †Department of Pharmacology, Center for Psychopharmacology, Diakonhjemmet Hospital, School of Pharmacy, University of Oslo, Blindern, Norway; ‡Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; and §Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Norway.
Ther Drug Monit. 2016 Feb;38(1):127-34. doi: 10.1097/FTD.0000000000000251.
To investigate the predictive value of the risperidone and venlafaxine metabolic ratios and CYP2D6 genotype.
The determination of risperidone, 9-hydroxyrisperidone, and venlafaxine, O-desmethylvenlafaxine, N-desmethylvenlafaxine and CYP2D6 genotype was performed in 425 and 491 patients, respectively. The receiver operator characteristic method and the area under the receiver operator characteristic curve were used to illustrate the predictive value of risperidone metabolic ratio for the individual CYP2D6 genotype. To evaluate the proposed cutoff levels of >1 to identify individuals with a poor CYP2D6 genotype, the sensitivity, specificity, positive predictive values, and negative predictive values were calculated.
Area under the receiver operator characteristic curve to predict poor metabolizers for risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine ratios was 93% and 99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value (confidence interval) of a risperidone/9-hydroxyrisperidone ratio >1 to predict a CYP2D6 poor metabolizer genotype were 91% (76%-97%), 86% (83%-89%), 35% (26%-46%), and 99% (97%-100%), respectively. The corresponding measures for N-desmethylvenlafaxine/O-desmethylvenlafaxine were 93% (76%-97%), 87% (83%-89%), 40% (32%-51%), and 99% (98%-100%).
Risperidone/9-hydroxyrisperidone and N-desmethylvenlafaxine/O-desmethylvenlafaxine metabolic ratios >1 strongly predict individuals with poor metabolizer genotype, which could guide psychotropic drug treatment to avoid adverse drug reactions and to increase their therapeutic efficacy in patients prescribed these drugs.
研究利培酮和文拉法辛代谢率及CYP2D6基因分型的预测价值。
分别对425例和491例患者进行了利培酮、9-羟基利培酮、文拉法辛、O-去甲基文拉法辛、N-去甲基文拉法辛的测定及CYP2D6基因分型。采用受试者工作特征法及受试者工作特征曲线下面积来说明利培酮代谢率对个体CYP2D6基因分型的预测价值。为评估提议的>1的截断水平以识别CYP2D6基因分型不佳的个体，计算了敏感性、特异性、阳性预测值和阴性预测值。
预测利培酮/9-羟基利培酮和N-去甲基文拉法辛/O-去甲基文拉法辛比值代谢不佳者的受试者工作特征曲线下面积分别为93%和99%。利培酮/9-羟基利培酮比值>1预测CYP2D6代谢不佳者基因型的敏感性、特异性、阳性预测值和阴性预测值（置信区间）分别为91%（76%-97%）、86%（83%-89%）、35%（26%-46%）和99%（97%-100%）。N-去甲基文拉法辛/O-去甲基文拉法辛的相应指标分别为93%（76%-97%）、87%（83%-89%）、40%（32%-51%）和99%（98%-100%）。
利培酮/9-羟基利培酮和N-去甲基文拉法辛/O-去甲基文拉法辛代谢率>1强烈预测代谢不佳者基因型个体，这可为精神药物治疗提供指导，以避免药物不良反应并提高服用这些药物患者的治疗效果。
