Barsegian S S, Maksimova T V, Morozov Iu E, Pleteneva T V, Salomatin E M, Tuchik E S
Sud Med Ekspert. 2014 Sep-Oct;57(5):40-6.
The objective of the present review was to analyse the problems of expert evaluation of the results of forensic chemical investigations of clozapine in the biological material. Such an analysis is needed because many topical aspects of the quantitative evaluation of toxic clozapine concentrations remain unclear. The treatment with clozapine is associated with its accumulation in blood in concentrations up to 2 mg/l in the absence of any toxic effect allegedly due to the development of tolerability of this agent. In the tolerant patients the ratio of the main clozapine metabolite, norclozapine, to clozapine itself in the serum amounts to 0.6-0.9. This value falls down to 0.3-0.4 in case of acute intoxication. In the case of identification of other pharmaceutical products narcotic drugs together with clozapine their influence on the activity of enzymes responsible for clozapine biotransformation should be taken into consideration. The concomitant intake of clozapine and alcohol may be dangerous for the clozapine-intolerant subjects. It is concluded that the above observations must be borne in mind in the assessment of the results of forensic chemical analysis.
本综述的目的是分析对生物材料中氯氮平法医化学调查结果进行专家评估时存在的问题。之所以需要进行这样的分析,是因为有毒氯氮平浓度定量评估的许多热点问题仍不明确。使用氯氮平治疗时,在据称由于对该药物产生耐受性而无任何毒性作用的情况下,其在血液中的浓度会累积至高达2mg/L。在耐受性患者中,血清中主要氯氮平代谢物去甲氯氮平与氯氮平本身的比例为0.6 - 0.9。在急性中毒时,该值降至0.3 - 0.4。在鉴定其他药品、麻醉药品与氯氮平同时存在的情况下,应考虑它们对负责氯氮平生物转化的酶活性的影响。氯氮平和酒精同时摄入对不耐受氯氮平的受试者可能是危险的。得出的结论是,在评估法医化学分析结果时必须牢记上述观察结果。