Moclobemide中毒:毒性动力学和发生的5 -羟色胺的毒性。
文章的细节
-
引用
复制到剪贴板 -
Isbister g·哈克特LP,道森啊,Whyte IM,史密斯AJ
Moclobemide中毒:毒性动力学和发生的5 -羟色胺的毒性。
Br中国新药杂志。2003年10月;56 (4):441 - 50。
- PubMed ID
-
12968990 (在PubMed]
- 文摘
-
目的:探讨频谱moclobemide过量的毒性,血清素毒性的发生,估计毒性动力学参数。方法:所有moclobemide过量给猎人在10年时间内区域综述了毒理学服务。临床特点、并发症、住院时间(LOS)和重症监护室(ICU)入学率从标准化提取,前瞻性收集的数据库。之间的比较是moclobemide单独和moclobemide羟色胺coingestant中毒。5 -羟色胺的毒性是由施特恩巴赫的标准和临床毒理学家的诊断。在五个病人连环moclobemide浓度测定。最大血浆浓度的时间(达峰时间),血浆浓度峰值(Cmax)和终端消除半衰期是估计的。结果:106年包括患者,33摄取moclobemide,仅21摄取moclobemide与另一个血清素激活的代理(在某些情况下,治疗剂量)和52摄取moclobemide nonserotonergic代理。coingesting 11(55%)的21例患者中血清素激活的药物开发的5 -羟色胺的毒性,这是大大超过一个(3%)的33 moclobemide-alone过量(优势比35岁,95%置信区间4,307;P < 0.0001)。 In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. CONCLUSIONS: The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.
DrugBank数据引用了这篇文章
- 药物