Le Bloc'h Yves, Woggon Brigitte, Weissenrieder Hansjörg, Brawand-Amey Marlyse, Spagnoli Jacques, Eap Chin B, Baumann Pierre
University Department of Adult Psychiatry, CH-1008 Prilly-Lausanne, Switzerland.
Ther Drug Monit. 2003 Oct;25(5):600-8. doi: 10.1097/00007691-200310000-00010.
From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications. Dose-corrected CIT plasma concentrations (C/D ratio) were 2.51 +/- 2.25 ng mL-1 mg-1 (n = 258; mean +/- SD). Patients >65 years had significantly higher dose-corrected CIT plasma concentrations (n = 56; 3.08 +/- 1.35 ng mL-1 mg-1) than younger patients (n = 195; 2.35 +/- 2.46 ng mL-1 mg-1) (P = 0.03). CIT plasma concentrations in the generally recommended dose range were [mean +/- SD, (median)]: 57 +/- 64 (45) ng/mL (10-20 mg/d; n = 64), 117 +/- 95 (91) ng/mL (21-60 mg/d; n = 96). At higher than usual doses, the following concentrations of CIT were measured: 61-120 mg/d CIT, 211 +/- 103 (190) ng/mL (n = 93); 121-200 mg/d: 339 +/- 143 (322) ng/mL (n = 70); 201-280 mg/d: 700 +/- 408 (565) ng/mL (n = 18); 281-360 mg/d: 888 +/- 620 (616) ng/mL (n = 4). When only one sample per patient (at the highest daily dose if repeated dosages) is considered, there is a linear and significant correlation (n = 48, r = 0.730; P < 0.001) between daily dose (10-200 mg/d) and CIT plasma concentrations. In experiments with dogs, DDCIT was reported to affect the QT interval when present at concentrations >300 ng/mL. In this study, DDCIT concentration reached 100 ng/mL in a patient treated with 280 mg/d CIT. Twelve other patients treated with 140-320 mg/d CIT had plasma concentrations of DDCIT within the range 52-73 ng/mL. In a subgroup comprised of patients treated with > or =160 mg/d CIT and with CIT plasma concentrations < or =300 ng/mL, and patients treated with < or =200 mg/d CIT and CIT plasma concentrations > or = 600 ng/mL, the enantiomers of CIT and DCIT were also analyzed. The highest S-CIT concentration measured in this subgroup was 327 ng/mL in a patient treated with 140 mg/d CIT, but the highest S-CIT concentration (632 ng/mL) was measured in patient treated with 360 mg/d CIT. In conclusion, there is a highly linear correlation between CIT plasma concentrations and CIT doses, well above the usual dose range.
从常规血药浓度监测（TDM）收集的数据中，测定了345份稳态条件下采集的血浆样本中舍曲林（CIT）及其代谢产物去甲基舍曲林（DCIT）和双去甲基舍曲林（DDCIT）的血浆浓度。这些样本来自258例接受常规剂量（20 - 60mg/d）治疗的患者以及接受80 - 360mg/d CIT治疗的患者。大多数患者有一种或几种合并用药，包括其他抗抑郁药、抗精神病药、锂盐、抗惊厥药、精神振奋药和躯体疾病用药。剂量校正后的CIT血浆浓度（C/D比值）为2.51±2.25ng mL⁻¹ mg⁻¹（n = 258；平均值±标准差）。65岁以上患者的剂量校正后CIT血浆浓度（n = 56；3.08±1.35ng mL⁻¹ mg⁻¹）显著高于年轻患者（n = 195；2.35±2.46ng mL⁻¹ mg⁻¹）（P = 0.03）。一般推荐剂量范围内的CIT血浆浓度为[平均值±标准差，（中位数）]：57±64（45）ng/mL（10 - 20mg/d；n = 64），117±95（91）ng/mL（21 - 60mg/d；n = 96）。高于常规剂量时，测得的CIT浓度如下：61 - 120mg/d CIT，211±103（190）ng/mL（n = 93）；121 - 200mg/d：339±143（322）ng/mL（n = 70）；201 - 280mg/d：700±408（565）ng/mL（n = 18）；281 - 360mg/d：888±620（616）ng/mL（n = 4）。当考虑每位患者仅一个样本（如果是重复给药则为最高日剂量时的样本）时，日剂量（10 - 200mg/d）与CIT血浆浓度之间存在线性且显著的相关性（n = 48，r = 0.730；P < 0.001）。在犬类实验中，据报道当DDCIT浓度>300ng/mL时会影响QT间期。在本研究中，一名接受280mg/d CIT治疗的患者中DDCIT浓度达到100ng/mL。另外12名接受140 - 320mg/d CIT治疗的患者血浆中DDCIT浓度在52 - 73ng/mL范围内。在一个亚组中，该亚组由接受≥160mg/d CIT治疗且CIT血浆浓度≤300ng/mL的患者以及接受≤200mg/d CIT治疗且CIT血浆浓度≥600ng/mL的患者组成，还分析了CIT和DCIT的对映体。在该亚组中测得的最高S - CIT浓度为一名接受140mg/d CIT治疗患者中的327ng/mL，但最高S - CIT浓度（632ng/mL）是在一名接受360mg/d CIT治疗的患者中测得的。总之，CIT血浆浓度与CIT剂量之间存在高度线性相关性，且远高于常规剂量范围。
