Oertel R, Pietsch J, Arenz N, Goltz L, Kirch W
Institut für klinische Pharmakologiel, Faculty of Medicine, Technical University, Dresden, Germany.
Pharmazie. 2011 Feb;66(2):115-8.
In forensic medicine autopsy material is primarily investigated to find out the cause of death. But the results of corresponding toxicology measurements often involve more information. With screening methods drugs were detected not being related to the cause of death. Liquid/liquid extraction and LC/MS/MS methods were used for the determination of drug concentrations. In seven cases metoprolol could be determined in different autopsy materials. In all cases the dosage of the drug was unknown. In cases with oral application probably the patients took a normal customary continuous dosage. Intoxication with metoprolol could be excluded in all cases. The concentrations of metoprolol in blood were all in the therapeutic range. The time between oral intake and death was unknown. Therefore and because of the low number of cases statistic calculations were not meaningful and an individual case study was necessary. In three cases the highest concentration of metoprolol was found in the liver. Probably, metoprolol was taken shortly before the person died. In the other cases the highest concentration of metoprolol was found in urine. This means the elimination process of the drug predominated at the time of death. In all cases the concentrations of metoprolol were similar in the compartments heart blood, venous blood and brain. In this study it was possible to measure the distribution of metoprolol in human directly in several compartments. Measurement of drug concentrations in human autopsy material deepen the knowledge of its pharmacokinetics.
在法医学中,尸检材料主要用于查明死因。但相应毒理学检测的结果往往包含更多信息。通过筛查方法检测到的药物与死因无关。采用液/液萃取和液相色谱/串联质谱法测定药物浓度。在7例尸检材料中可检测到美托洛尔。所有病例中药物剂量均未知。口服给药的病例中,患者可能服用的是正常习惯的持续剂量。所有病例均可排除美托洛尔中毒。血液中美托洛尔的浓度均在治疗范围内。口服摄入与死亡之间的时间未知。因此,由于病例数量较少,统计计算无意义,有必要进行个案研究。3例病例中,肝脏中美托洛尔浓度最高。可能在患者死亡前不久服用了美托洛尔。其他病例中,尿液中美托洛尔浓度最高。这意味着在死亡时药物的消除过程占主导。所有病例中心脏血、静脉血和脑组织中美托洛尔浓度相似。在本研究中,可以直接测量人体多个部位中美托洛尔的分布情况。对人体尸检材料中药物浓度的测量加深了对其药代动力学的认识。