Syvälahti E K, Taiminen T, Saarijärvi S, Lehto H, Niemi H, Ahola V, Dahl M L, Salokangas R K
Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.
J Int Med Res. 1997 Jan-Feb;25(1):24-32. doi: 10.1177/030006059702500104.
Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of citalopram and its main metabolite, desmethylcitalopram, were also measured. In addition, patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors. There were no significant changes in plasma concentrations of haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or perphenazine during the study. Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy, and remained stable throughout the study. None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that clinically important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients.
在90例精神分裂症患者的治疗方案中添加安慰剂或西酞普兰（40毫克/天）之前和之后，测量了常用抗精神病药物的稳态血浆浓度。还测量了西酞普兰及其主要代谢产物去甲西酞普兰的血浆浓度。此外，对在12周研究期间抗精神病药物水平异常高或不良反应增加的患者进行了异喹胍/司巴丁羟化酶（CYP2D6）基因型评估，该酶负责几种抗精神病药物和选择性5-羟色胺再摄取抑制剂的氧化代谢。在研究期间，氟哌啶醇、氯丙嗪、珠氯噻醇、左美丙嗪、硫利达嗪或奋乃静的血浆浓度没有显著变化。西酞普兰和去甲西酞普兰的血浆浓度完全在先前报道的单一疗法水平范围内，并且在整个研究过程中保持稳定。分析的15例CYP2D6基因型患者中没有代谢不良者。得出的结论是，当西酞普兰用作抗精神病药物治疗的精神分裂症患者的增效疗法时，临床上重要的药代动力学药物相互作用不起关键作用。
