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门诊环境中艾司西酞普兰的治疗药物监测

Therapeutic drug monitoring of escitalopram in an outpatient setting.

作者信息

Reis Margareta, Chermá Maria D, Carlsson Björn, Bengtsson Finn

机构信息

Department of Clinical Pharmacology, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden.

出版信息

Ther Drug Monit. 2007 Dec;29(6):758-66. doi: 10.1097/FTD.0b013e31815b3f62.

Abstract

The main objectives of this study were to outline the inter- and intraindividual and overall pharmacokinetic variability of S-citalopram, S-desmethylcitalopram, and S-didesmethylcitalopram in serum by means of therapeutic drug monitoring; and to investigate potential correlations between the serum concentration and simultaneously collected clinical data. The study was conducted on outpatients in Sweden in 2002 to 2005. Included in the pharmacokinetic evaluation were 155 patients (68% women and 32% men) aged 17 to 95 years (average, 51 years). One serum sample per patient, taken as a trough value in steady state, was assessed. For the inter- and intraindividual variation calculation, 16 patients were included with two eligible samples each. The median daily dose was 20 mg/day (range, 5-40 mg). Extensive overall serum concentration variability was seen for all dose levels. The interindividual coefficient of variation for dose-normalized concentrations was 71% for S-citalopram, 36% for S-desmethylcitalopram, and 50% for S-didesmethylcitalopram. The intraindividual variations over time for the same parameters were approximately 30%, except for the ratio S-desmethylcitalopram/S-citalopram, which was 23%. The median S-desmethylcitalopram level was approximately 60% of the parent substance and the S-didesmethylcitalopram level approximately 9%. Higher age was correlated with higher serum concentrations, but no gender-related concentration differences were found. A majority (76%) of the patients took one or more drugs in addition to escitalopram, but concomitant medication did not seem to interact with escitalopram. However, women taking oral contraceptives showed a lower metabolic ratio compared with age-matched women. As a result of the wide range of the ratio in this population, these findings are not considered of clinical relevance.

摘要

本研究的主要目的是通过治疗药物监测概述血清中S-西酞普兰、S-去甲基西酞普兰和S-双去甲基西酞普兰的个体间、个体内及总体药代动力学变异性;并研究血清浓度与同时收集的临床数据之间的潜在相关性。该研究于2002年至2005年在瑞典的门诊患者中进行。纳入药代动力学评估的有155例患者(68%为女性,32%为男性),年龄在17至95岁之间(平均51岁)。评估了每位患者在稳态时作为谷值采集的一份血清样本。为计算个体间和个体内变异,纳入了16例患者,每人有两份合格样本。日剂量中位数为20mg/天(范围为5 - 40mg)。在所有剂量水平下均观察到广泛的总体血清浓度变异性。S-西酞普兰剂量标准化浓度的个体间变异系数为71%,S-去甲基西酞普兰为36%,S-双去甲基西酞普兰为50%。除S-去甲基西酞普兰/S-西酞普兰比值为23%外,相同参数随时间的个体内变异约为30%。S-去甲基西酞普兰水平中位数约为母体物质的60%,S-双去甲基西酞普兰水平约为9%。年龄较大与血清浓度较高相关,但未发现与性别相关的浓度差异。大多数(76%)患者除艾司西酞普兰外还服用了一种或多种药物,但合并用药似乎未与艾司西酞普兰相互作用。然而,服用口服避孕药的女性与年龄匹配的女性相比,代谢比值较低。由于该人群中该比值范围较宽,这些发现不被认为具有临床相关性。

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