Gjestad Caroline, Westin Andreas A, Skogvoll Eirik, Spigset Olav
*Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim; †Department of Pharmaceutical Bioscience, School of Pharmacy, University of Oslo; ‡Department of Anaesthesiology and Critical Care, St. Olav University Hospital; §Department of Circulation and Medical Imaging, Norwegian University of Science and Technology; and ¶Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
Ther Drug Monit. 2015 Feb;37(1):90-7. doi: 10.1097/FTD.0000000000000101.
The selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, and sertraline are all metabolized by the cytochrome P-450 isoenzyme CYP2C19, which is inhibited by the proton pump inhibitors (PPIs) omeprazole, esomeprazole, lansoprazole, and pantoprazole. The aim of the present study was to evaluate the effect of these PPIs on the serum concentrations of citalopram, escitalopram, and sertraline.
Serum concentrations from patients treated with citalopram, escitalopram, or sertraline were obtained from a routine therapeutic drug monitoring database, and samples from subjects concomitantly using PPIs were identified. Dose-adjusted SSRI serum concentrations were calculated to compare data from those treated and those not treated with PPIs.
Citalopram concentrations were significantly higher in patients treated with omeprazole (+35.3%; P < 0.001), esomeprazole (+32.8%; P < 0.001), and lansoprazole (+14.7%; P = 0.043). Escitalopram concentrations were significantly higher in patients treated with omeprazole (+93.9%; P < 0.001), esomeprazole (+81.8%; P < 0.001), lansoprazole (+20.1%; P = 0.008), and pantoprazole (+21.6%; P = 0.002). Sertraline concentrations were significantly higher in patients treated with esomeprazole (+38.5%; P = 0.0014).
The effect of comedication with PPIs on the serum concentration of SSRIs is more pronounced for omeprazole and esomeprazole than for lansoprazole and pantoprazole, and escitalopram is affected to a greater extent than are citalopram and sertraline. When omeprazole or esomeprazole are used in combination with escitalopram, a 50% dose reduction of the latter should be considered.
选择性5-羟色胺再摄取抑制剂（SSRI）西酞普兰、艾司西酞普兰和舍曲林均通过细胞色素P-450同工酶CYP2C19代谢，质子泵抑制剂（PPI）奥美拉唑、埃索美拉唑、兰索拉唑和泮托拉唑可抑制该酶。本研究旨在评估这些PPI对西酞普兰、艾司西酞普兰和舍曲林血清浓度的影响。
从常规治疗药物监测数据库中获取接受西酞普兰、艾司西酞普兰或舍曲林治疗患者的血清浓度，并识别同时使用PPI患者的样本。计算剂量调整后的SSRI血清浓度，以比较接受PPI治疗患者与未接受PPI治疗患者的数据。
接受奥美拉唑（升高35.3%；P<0.001）、埃索美拉唑（升高32.8%；P<0.001）和兰索拉唑（升高14.7%；P=0.043）治疗的患者，其西酞普兰浓度显著更高。接受奥美拉唑（升高93.9%；P<0.001）、埃索美拉唑（升高81.8%；P<0.001）、兰索拉唑（升高20.1%；P=0.008）和泮托拉唑（升高21.6%；P=0.002）治疗的患者，其艾司西酞普兰浓度显著更高。接受埃索美拉唑治疗的患者，其舍曲林浓度显著更高（升高38.5%；P=0.0014）。
与兰索拉唑和泮托拉唑相比，PPI与SSRI联合用药对SSRI血清浓度的影响在奥美拉唑和埃索美拉唑中更为显著，且艾司西酞普兰受到的影响程度大于西酞普兰和舍曲林。当奥美拉唑或埃索美拉唑与艾司西酞普兰联合使用时，应考虑将后者的剂量减少50%。
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