Stedman Catherine A M, Begg Evan J, Kennedy Martin A, Roberts Rebecca, Wilkinson Timothy J
Department of Clinical Pharmacology, Christchurch Hospital, Christchurch School of Medicine, Christchurch, New Zealand.
Hum Psychopharmacol. 2002 Jun;17(4):187-90. doi: 10.1002/hup.394.
The aims of this study were to determine if patients with SSRI-related hyponatraemia were (1) genetically poor metabolizers of CYP2D6, and/or (2) had excessive plasma concentrations of the SSRI antidepressant.
Plasma DNA from 20 people with hyponatraemia attributable to fluoxetine or paroxetine was analysed for the CYP2D6 alleles *1-*16. Trough plasma concentrations of fluoxetine and norfluoxetine, or paroxetine were assayed in nine people who remained on the antidepressant.
Genotype results were compared with those published in a large population study. The poor metabolizer PM/PM genotype was present in one subject only, or 5% of the study population, compared with 7.2% of a general population. The 95% Cl of this result was 0-21%, suggesting that it is most unlikely that hyponatremia is related to the PM/PM genotype. The intermediate IM/PM genotype was present in 5% compared with 19.7% of a general population. All differences were not statistically significant. Antidepressant concentrations of fluoxetine (n = 5, all EM) and paroxetine (n = 1 IM/PM and n = 3 EM) were all within the lower half of the reference range.
These results do not support the hypothesis that SSRI-related hyponatraemia is linked to genetically poor metabolizers, or excessive drug concentrations.
本研究旨在确定患有与选择性5-羟色胺再摄取抑制剂（SSRI）相关低钠血症的患者是否（1）是细胞色素P450 2D6（CYP2D6）的基因慢代谢者，和/或（2）血浆中SSRI抗抑郁药浓度过高。
对20名因氟西汀或帕罗西汀导致低钠血症患者的血浆DNA进行CYP2D6等位基因*1-*16分析。对9名继续服用抗抑郁药患者的氟西汀、去甲氟西汀或帕罗西汀的血浆谷浓度进行检测。
将基因型结果与一项大型人群研究中公布的结果进行比较。仅1名受试者（即研究人群的5%）存在慢代谢者PM/PM基因型，而普通人群中这一比例为7.2%。该结果的95%置信区间为0-21%，表明低钠血症极不可能与PM/PM基因型有关。中间型IM/PM基因型的比例为5%，而普通人群中这一比例为19.7%。所有差异均无统计学意义。氟西汀（n = 5，均为快代谢者）和帕罗西汀（n = 1为IM/PM型，n = 3为快代谢者）的抗抑郁药浓度均在参考范围的下半部分。
这些结果不支持SSRI相关低钠血症与基因慢代谢者或药物浓度过高有关的假说。
