Aims and Objective: The plasma level of mirtazapine (MIR) varies between individuals primarily depending on the differences in metabolism during pharmacotherapy. CYP2D6 takes the role as a major enzyme in MIR metabolism and POR enzyme donates an electron to CYP2D6 for its activity. Single nucleotide polymorphisms in the genes encoding pharmacokinetic enzymes may cause changes in enzyme activity, leading to differences in metabolism of the drug. Our aim was to assess the influence of CYP2D6*4 and POR*28 polymorphisms on MIR plasma levels in Turkish psychiatric patients.

Materials and Methods: The association between genetic variations and plasma level of MIR was investigated on 54 patients. CYP2D6*4 and POR*28 polymorphisms were analysed using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) and plasma MIR levels were measured using HPLC.

Results: Allele frequencies of CYP2D6*4 and POR*28 were 0.11 and 0.39, respectively in the study population. The results showed that CYP2D6*4 allele carriers have higher C/D MIR levels while POR*28 allele carriers have lower C/D MIR levels. Combined genotype analyses also revealed that individuals with CYP2D6*1/*1 - POR*28/*28 genotype have a statistically lower C/D MIR level (0.95 ng/ml/dose) when compared with individuals with CYP2D6*1/*1 - POR*1/*1 genotype (1.52 ng/ml/dose).

Conclusion: Our results indicate that CYP2D6*4 and POR*28 polymorphisms may have a potential in the explanation of differences in plasma levels in MIR treated psychiatric patients. A combination of these variations may be beneficial in increasing drug response and decreasing adverse drug reactions in MIR psychopharmacotherapy.

目的和目的：米氮平（MIR）的血浆水平因人而异，主要取决于药物治疗期间新陈代谢的差异。CYP2D6在MIR代谢中起主要酶的作用，POR酶则向CYP2D6贡献电子。编码药代动力学酶的基因中的单核苷酸多态性可能会引起酶活性的变化，从而导致药物代谢的差异。我们的目的是评估CYP2D6 * 4和POR * 28多态性对土耳其精神病患者MIR血浆水平的影响。

材料与方法：研究了54例患者的MIR遗传变异与血浆水平之间的相关性。用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析CYP2D6 * 4和POR * 28的多态性，并用HPLC测量血浆MIR水平。

结果：研究人群中CYP2D6 * 4和POR * 28的等位基因频率分别为0.11和0.39。结果表明，CYP2D6 * 4等位基因携带者具有较高的C / D MIR水平，而POR * 28等位基因携带者具有较低的C / D MIR水平。联合基因型分析还显示，与具有CYP2D6 * 1 / * 1的个体相比，具有CYP2D6 * 1 / * 1-POR * 28 / * 28基因型的个体具有统计学上较低的C / D MIR水平（0.95 ng / ml /剂量） -POR * 1 / * 1基因型（1.52 ng / ml /剂量）。

结论：我们的结果表明，CYP2D6 * 4和POR * 28基因多态性可能解释MIR治疗的精神病患者血浆水平的差异。这些变化的组合可能有助于提高MIR心理药物疗法的药物反应和减少药物不良反应。