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死后对乙酰氨基酚的药代动力学:一项关于部位和时间依赖性浓度变化的实验研究

Postmortem acetaminophen pharmacokinetics: an experimental study of site and time-dependent concentration changes.

作者信息

Gomez H F, McKinney P, Phillips S, Roberts D V, Brent J, Watson W A

机构信息

Rocky Mountain Poison and Drug Center, Denver General Hospital, University of Colorado Health Science Center, USA.

出版信息

J Forensic Sci. 1995 Nov;40(6):980-2.

PMID:8522929
Abstract

Postmortem blood drug concentrations are obtained routinely for assessment of the cause of mortality. However, the relationship of postmortem drug concentration to blood concentrations at the time of death remains poorly characterized. Using Ketamine sedation, 10 New Zealand white rabbits were sacrificed 20 minutes after oral gavage with liquid acetaminophen 160 mg/kg as a model drug. Blood samples were obtained from peripheral (femoral vein) and central sites (heart & inferior cava) over time and compared with heart blood concentrations obtained at the time of sacrifice. The mean +/- SE antemortem acetaminophen concentration was 63.1 +/- 14.6 mcg/ml. Postmortem central blood concentrations were as follows: T = 3 h: 200.8 +/- 129.2 micrograms/mL, T = 6 h: 100.8 +/- 39.6 micrograms/mL and T = 12 h: 480.8 +/- 128.8 micrograms/mL. Postmortem peripheral site results were: T = 3 h: 50.2 +/- 21.4 micrograms/mL, T = 6 h: 100.8 +/- 18.1 and T = 12 h: 117.7 +/- 37.2 micrograms/mL. Overall, blood acetaminophen concentrations increased significantly over time for central sampling sites. Drug concentration increases seen in the central sampling sites were several times higher than that seen in peripheral blood. Blood samples taken from peripheral sites did not alter significantly. The results of this controlled study were consistent with previous autopsy case series and case reports suggesting that postmortem drug concentrations do not reflect premortem values. Variables affecting postmortem drug concentrations include both postmortem sampling time and anatomic blood collection site.

摘要

尸检时常规获取血液药物浓度以评估死亡原因。然而,尸检药物浓度与死亡时血液浓度之间的关系仍未得到充分描述。使用氯胺酮镇静,以160mg/kg液体对乙酰氨基酚经口灌胃后20分钟,处死10只新西兰白兔作为模型药物。随时间从外周(股静脉)和中心部位(心脏和下腔静脉)采集血样,并与处死时获得的心脏血浓度进行比较。死前对乙酰氨基酚平均浓度为63.1±14.6μg/ml。死后中心血浓度如下:T = 3小时:200.8±129.2μg/mL,T = 6小时:100.8±39.6μg/mL,T = 12小时:480.8±128.8μg/mL。死后外周部位结果为:T = 3小时:50.2±21.4μg/mL,T = 6小时:100.8±18.1μg/mL,T = 及12小时:117.7±37.2μg/mL。总体而言,中心采样部位的血液对乙酰氨基酚浓度随时间显著增加。中心采样部位观察到的药物浓度增加比外周血中观察到的高出几倍。从外周部位采集的血样没有明显变化。这项对照研究的结果与先前的尸检病例系列和病例报告一致,表明死后药物浓度不能反映死前值。影响死后药物浓度的变量包括死后采样时间和解剖学采血部位。

相似文献

1
Postmortem acetaminophen pharmacokinetics: an experimental study of site and time-dependent concentration changes.死后对乙酰氨基酚的药代动力学:一项关于部位和时间依赖性浓度变化的实验研究
J Forensic Sci. 1995 Nov;40(6):980-2.
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Postmortem drug redistribution--human cases related to results in experimental animals.死后药物再分布——与实验动物结果相关的人类案例
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Vitreous humor cocaine and metabolite concentrations: do postmortem specimens reflect blood levels at the time of death?玻璃体液中可卡因及其代谢物的浓度:死后标本能否反映死亡时的血液水平?
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Post-mortem redistribution of three beta-blockers in the rabbit.三种β受体阻滞剂在兔体内的死后再分布
Int J Legal Med. 2006 Jul;120(4):226-32. doi: 10.1007/s00414-005-0022-5. Epub 2005 Oct 25.
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Estimating antemortem drug concentrations from postmortem blood samples: the influence of postmortem redistribution.从死后血液样本估计生前药物浓度:死后再分布的影响。
J Clin Pathol. 2000 Apr;53(4):282-5. doi: 10.1136/jcp.53.4.282.