Influence of blood loss on the pharmacokinetics of citalopram
Influence of blood loss on the pharmacokinetics of citalopram
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DOI：
10.1016/j.forsciint.2006.02.050
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发表时间：
2006-09-12
影响因子：
2.2
通讯作者：
Carlsson, Bjorn
中科院分区：
文献类型：
--
作者：
Kugelberg, Fredrik C.;Alkass, Kanar;Carlsson, Bjorn
长期失血导致几种代偿性生理机制，包括将血管外液体转移到血液循环中。如果药物存在于体内，这种液体交换可能意味着在创伤受害者中发现的血液药物浓度可能不同于创伤时存在的浓度。为了解决这个问题，使用动物模型来研究失血对抗抑郁药物西酞普兰及其去甲基代谢物的预先存在水平的影响。使用渗透泵对大鼠急性（40 mg/kg，口服）或慢性（20 mg/kg，每日，皮下）给予西酞普兰6天。在实验大鼠中，通过在70分钟内每隔10分钟抽取0.8 mL血液来完成失血。在对照大鼠中，仅在0和70分钟抽取血液。血液，脑和肺的药物浓度进行了分析与对映体选择性HPLC方法。在长期治疗的大鼠中，实验大鼠和对照组的最终和初始西酞普兰浓度之比分别为1.08 +/- 0.15和1.01 +/- 0.09，表明失血没有重大影响。相比之下，与对照组相比，急性经口给药导致放血大鼠中的比值增加（1.84 +/- 0.50 vs 0.73 +/- 0.07; p = 0.0495）。总之，观察到急性经口给药大鼠血液药物水平升高，表明胃肠道液体吸收可能在血管内再充盈中起重要作用。此外，在解释死后血液中的药物水平时，应考虑这些生理机制。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Extended blood loss results in several compensatory physiological mechanisms, including transfer of extravascular fluid into the blood circulation. If drugs are present in the body, this fluid exchange may imply that blood drug concentrations found in a trauma victim may differ from the concentrations present at the time of the trauma. To address this issue, an animal model was used to investigate the influence of blood loss on pre-existing levels of the antidepressant drug citalopram and its demethylated metabolites. Rats were administered citalopram either acutely (40 mg/kg, orally) or chronically (20 mg/kg daily, subcutaneously) for 6 days using osmotic pumps. In the experimental rats, blood loss was accomplished by withdrawing 0.8 mL blood at 10 min intervals during 70 min. In the control rats, blood was withdrawn at 0 and 70 min only. Blood, brain and lung drug concentrations were analyzed with an enantioselective HPLC method. In the chronically treated rats, the ratios between final and initial citaloprain concentrations were 1.08 +/- 0.15 and 1.01 +/- 0.09 in the experimental rats and controls, respectively, indicating no major effect of blood loss. In contrast, acute oral administration resulted in increased ratios in the exsanguinated rats as compared to controls (1.84 +/- 0.50 versus 0.73 +/- 0.07; p = 0.0495). In conclusion, the observation of increased blood drug levels in the acute oral rats indicates that absorption of fluid from the gastrointestinal tract may be important in the intravascular refill. Further, in the interpretation of post-mortem blood levels of drugs, these physiological mechanisms should be taken into account. (c) 2006 Elsevier Ireland Ltd. All rights reserved.