Postmortem diffusion of drugs from gastric residue: an experimental study.
Postmortem diffusion of drugs from gastric residue: an experimental study.
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胃残留物的死后药物扩散：一项实验研究。
DOI：
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发表时间：
1996
影响因子：
1
通讯作者：
N. Kuroda
中科院分区：
文献类型：
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作者：
D. Pounder;C. Fuke;D. E. Cox;D. Smith;N. Kuroda
在人体尸体模型中评估了胃残留物的死后药物扩散。50毫克阿米替林（Ami）和5克扑热息痛（Par）悬浮在350毫升10%甲醇、0.1盐酸和50毫升尿路素中，加5克碳酸锂（碱性模型）或不加锂（酸性模型），经食管管经颈部解剖注入胃中。在室温下（平均小时室温范围：15.6-20.7℃，n = 9） 48小时后获得多个样品。胃内容物pH（碱性模型范围8.3 ~ 8.9,n = 5；酸性模型范围3.4 ~ 3.8,n = 5）无显著影响。药物扩散在左肺底部最为明显，Ami的药物浓度（微克/g）为0.1 ~ 13.9，Par为65 ~ 524，锂为13 ~ 161。同样受到影响的还有肝左叶（Ami, 0.1-54.9; Par, 7-218；锂，7-39）、脾脏（Ami, 0.6-24.3; Par, 104-663；锂，27-106）和心包液（Ami, 0-4.5; Par, 48-641；锂，12-56）。扩散到胆囊胆汁、心脏血液、主动脉血液和下腔静脉血液的情况较轻。左肾和左肺比右肾和右肺更严重，左腰肌和右腰肌也是如此。影响最小的是右肝前叶和肺尖。这种现象可能显著影响肝脏和躯干血液样本中的药物浓度，从而影响肝脏/血液药物比率。为了避免死后药物从胃扩散的问题，建议从周围血管取样，从肢体骨骼肌取样，从右叶深处取样肝脏，从肺尖而不是肺底取样。
Postmortem drug diffusion from gastric residue was assessed in a human cadaver model. Fifty milligrams of amitriptyline (Ami) and 5 g of paracetamol (Par) suspended in 350 ml of 10% methanol, 0.1 N HCl, and 50 ml urograffin with 5 g lithium carbonate (alkaline model) or without lithium (acidic model) was instilled into the stomach through an esophageal tube via a neck dissection. Multiple samples were obtained after 48 h at room temperature (range in mean hourly room temperature: 15.6-20.7 degrees C, n = 9). The pH of the gastric contents (alkaline model range = 8.3-8.9, n = 5; acidic model range = 3.4-3.8, n = 5) had no significant effect. Drug diffusion was most marked in the left lung base, with drug concentrations (micrograms/g) of 0.1-13.9 for Ami, 65-524 for Par, and 13-161 for lithium. Similarly affected were the left lobe of the liver (Ami, 0.1-54.9; Par, 7-218; lithium, 7-39), the spleen (Ami, 0.6-24.3; Par, 104-663; lithium, 27-106), and pericardial fluid (Ami, 0-4.5; Par, 48-641; lithium, 12-56). Diffusion into gallbladder bile, cardiac blood, aortic blood, and blood of the inferior vena cava was less severe. The left kidney and left lung were more severely affected than the right kidney and lung, and similarly the left and right psoas muscles. Least affected was the right anterior lobe of the liver and the lung apexes. This phenomenon may significantly influence drug concentrations in liver and in blood samples obtained from the torso, and consequently liver/blood drug ratios. To circumvent the problem of postmortem drug diffusion from the stomach, it is recommended that blood be sampled from a peripheral vessel, skeletal muscle from a limb, liver from deep within the right lobe, and lung from the apex rather than the base.