Pollak P T, Zbuk K
Department of Medicine, Queen Elizabeth II HSC, Dalhousie University, Halifax, Nova Scotia, Canada.
Clin Pharmacol Ther. 2000 Jul;68(1):92-7. doi: 10.1067/mcp.2000.107507.
Although the new atypical antipsychotic, quetiapine fumarate, is growing in popularity over its progenitor, clozapine, clinical experience with overdose of this agent remains limited. Observation of an overdose situation provided a unique opportunity to define the safety, clinical effects, and pharmacokinetics of this medication more clearly.
A patient admitted immediately after ingesting an overdose of 30 tablets of 100 mg of quetiapine was observed carefully to document effects of the medication. These observations were compared with the only two other published cases of overdose, to the known pharmacology of the drug, and to serial measurements of serum drug concentrations obtained to document the time course of elimination of the drug.
Consistent with the two previously published cases, the main clinical effects of overdose were hypotension, tachycardia, and somnolence as predicted by its known alpha-adrenergic receptor and histamine receptor blockade. These effects were managed with fluid resuscitation and supportive measures. No cardiac arrhythmias other than tachycardia have been reported, but the tachycardia was of an unexpectedly long duration in this case. Decline in serum quetiapine concentration followed a biexponential pattern with a terminal elimination half-life of 22 hours. Unexpectedly low peak serum concentrations in three patients with overdose suggest that absorption is highly reduced, either by the effects of the overdose or by the activated charcoal administered.
Quetiapine appears to have greater safety in overdose than traditional antipsychotic agents. Its toxicity is consistent with its receptor pharmacology. Elevated serum concentrations associated with this overdose remained above the limit of detection long enough to document a terminal elimination half-life of 22 hours in this patient. This is much more consistent with previously noted duration of clinical effects and detectable serum concentrations after overdose than the published half-life of 6 hours. Physicians should be aware that any new drug that is active at low concentrations may have had its half-life underestimated during preclinical development because of the difficulty in detecting the drug after the distribution phase has ended.
尽管新型非典型抗精神病药物富马酸喹硫平的使用比其前身氯氮平更为普遍，但关于该药物过量服用的临床经验仍然有限。观察一次过量用药情况为更清晰地界定该药物的安全性、临床效果及药代动力学提供了一个独特的机会。
一名患者在过量服用30片100毫克的喹硫平后立即入院，对其进行了仔细观察以记录该药物的效果。将这些观察结果与另外仅有的两例已发表的过量用药病例、该药物已知的药理学情况以及为记录药物消除时间过程而进行的血清药物浓度系列测量结果进行了比较。
与之前发表的两例病例一致，过量服用的主要临床效果为低血压、心动过速和嗜睡，正如其已知的α-肾上腺素能受体和组胺受体阻断作用所预测的那样。这些症状通过液体复苏和支持性措施得到了处理。除心动过速外未报告有心律失常，但该病例中的心动过速持续时间出乎意料地长。血清喹硫平浓度呈双指数下降模式，终末消除半衰期为22小时。三名过量用药患者的血清峰值浓度意外地低，这表明吸收因过量用药的影响或因给予活性炭而大幅降低。
喹硫平过量服用时似乎比传统抗精神病药物具有更高的安全性。其毒性与其受体药理学一致。与此次过量服用相关的血清浓度升高在足够长的时间内保持在检测限以上，从而记录到该患者的终末消除半衰期为22小时。这与之前所指出的过量服用后的临床效果持续时间和可检测血清浓度比已发表的6小时半衰期更为一致。医生应意识到，任何在低浓度下有活性的新药在临床前开发期间其半衰期可能因在分布阶段结束后难以检测到该药物而被低估。
