Therapeutic drug monitoring of racemic citalopram: A 5-year experience in Sweden, 1992-1997
Therapeutic drug monitoring of racemic citalopram: A 5-year experience in Sweden, 1992-1997
复制标题
DOI：
10.1097/00007691-200304000-00007
复制
发表时间：
2003-04-01
影响因子：
2.5
通讯作者：
Bengtsson, F
中科院分区：
文献类型：
--
作者：
Reis, M;Lundmark, M;Bengtsson, F
外消旋西酞普兰 (CIT) 于 1992 年在瑞典推出，用于治疗重度抑郁症。在 1992 年至 1997 年的 5 年期间，从瑞典各地的患者中收集了 CIT 和去甲基西酞普兰 (DCIT) 的血清样本，用于治疗药物监测 (TDM)。这些样本附有专门设计的 TDM 申请表上的临床信息。他们代表不同年龄（11-94 岁）的男性和女性，通常同时服用多种药物并在自然环境中接受治疗。对符合评估条件的 TDM 样品 (n = 749)（所有稳态谷值）进行了个体间和个体内药代动力学变异性的研究。在所有剂量水平上都观察到广泛的个体间血清浓度变异性。对于剂量校正浓度 (C/D) 和清除率 (CI)，我们发现所有变量（C/D CIT、C/D DCIT、DCIT 与 CIT 的比率以及 CI CIT）的变异系数 (CV) 约为 55%。相同参数随时间的个体差异为 30% 至 35%。在人群水平上，观察到 CYP2D6 可能饱和的迹象，该迹象与随着日剂量增加而增加的 DCIT 与 CIT 比率相关。年龄和性别影响 CIT 和 DCIT 的药代动力学。与男性相比，女性的 C/D CIT 和 C/D DCIT 显着较高，而 Cl CIT 值较低；与年轻患者相比，65 岁以上患者的 C/D CIT 和 C/D DCIT 较高，Cl CIT 值较低。最后，伴随药物通过 C/D CIT 和 C/D DCIT 普遍增加影响血清浓度结果，但不改变 DCIT 与 CIT 比率。因此，当使用多种药物（并且多种疾病流行？）时，CIT 处置的这种变化趋势在性质上似乎更普遍，而不是特定于某种药物或某种药物。
Racemic citalopram (CIT) was introduced in Sweden in 1992 for management of major depression. During a 5-year period, 1992 to 1997, serum samples of CIT and desmethylcitalopram (DCIT) were collected for therapeutic drug monitoring (TDM) from patients from all over Sweden. These samples were accompanied by clinical information on a specially designed TDM request form. They represented men and women of various ages (11-94 years) usually on multiple concomitant medications and treated in a naturalistic setting. The TDM samples eligible for evaluation (n = 749), all trough values at steady state, were studied with respect to inter- and intraindividual pharmacokinetic variability. Extensive, interindividual serum concentration variability was seen on all dose levels. For dose-corrected concentrations (C/D) and for clearance (CI) we found the coefficient of variation (CV) to be approximately 55% for all variables (C/D CIT, C/D DCIT, the ratio DCIT to CIT, and for CI CIT). The intraindividual variations over time for the same parameters were 30% to 35%. On a population level, signs of a possible saturation of CYP2D6 associated with increasing DCIT-to-CIT ratios with increasing daily doses was observed. Age and gender affected the pharmacokinetics of CIT and DCIT. Women showed significantly higher C/D CIT and C/D DCIT and lower Cl CIT values compared with men, and patients aged more than 65 years had higher C/D CIT and C/D DCIT and lower Cl CIT values compared with younger patients. Finally, concomitant medication affected the outcome of serum concentrations by a general increase in C/D CIT and C/D DCIT but without alteration in the DCIT-to-CIT ratio. Thus, this tendency of changes in the CIT disposition when multiple drugs are used (and multiple diseases are prevailing?) seems more general in character than specific for a certain drug or type of drugs.