Department of Research & Education in Psychiatry, Diakonhjemmet Hospital, Oslo, Norway.
Pharmacopsychiatry. 2010 Jul;43(5):190-3. doi: 10.1055/s-0030-1254106. Epub 2010 May 25.
The antidepressive effect of racemic citalopram (CIT) is exerted by S-CIT, while R-CIT is a partial antagonist to S-CIT. Since R-and S-CIT are metabolized by different pathways, we investigated whether the ratio of S- and R-CIT may differ between individuals on the same dose of racemic CIT, and if a possible variability in the R/S-ratio could be dose-dependent.
A chiral analysis of R- and S-CIT in serum samples taken from 88 female patients receiving treatment with racemic CIT was performed using high-pressure liquid chromatography.
The mean levels of R-CIT were significantly higher than those of S-CIT in all dose groups. The R/S-CIT ratio increased from 1.99 to 2.45 with an increase in the dose (p<0.05), and the interindividual variance in the R/S-CIT ratio was up to four-fold on the same dosage.
Our findings show that the stereoselective metabolism of citalopram IN VIVO has pharmacokinetic consequences reflected by dose dependent variations of enantiomeric drug concentrations, as well as substantial interindividual variabilities in the ratios of the concentrations. The clinical consequences, however, are unclear and should be further explored.
消旋西酞普兰（CIT）的抗抑郁作用是由 S-CIT 发挥的，而 R-CIT 是 S-CIT 的部分拮抗剂。由于 R-和 S-CIT 通过不同的途径代谢，我们研究了在相同剂量的消旋 CIT 下，个体之间 S-和 R-CIT 的比例是否不同，以及 R/S 比值的可能变化是否与剂量有关。
使用高压液相色谱法对 88 名接受消旋 CIT 治疗的女性患者的血清样本中的 R-和 S-CIT 进行了手性分析。
在所有剂量组中，R-CIT 的平均水平均明显高于 S-CIT。随着剂量的增加，R/S-CIT 比值从 1.99 增加到 2.45（p<0.05），并且在相同剂量下个体间的 R/S-CIT 比值差异高达四倍。
我们的发现表明，西酞普兰在体内的立体选择性代谢具有药代动力学后果，反映在对映体药物浓度的剂量依赖性变化以及浓度比值的个体间显著差异上。然而，其临床后果尚不清楚，应进一步探讨。
