Фармакокінетика етанолу в світлі інтересів судової медицини

Abstract

Стаття присвячена аналізу літературних джерел, що стосуються фармакокінетики етанолу з акцентуванням уваги на тих моментах, які мають практичне значення для судової медицини. Показано, що ретроградна екстраполяція і визначення рівня алкоголю в організмі на певний момент часу до відбирання зразків біоматеріалу проводиться шляхом інтерпретації даних про абсорбцію, розподіл та елімінацію етанолу, його взаємодію з лікарськими засобами та наркотичними речовинами. За цих умов підвищення індивідуалізації й точності діагностики можливе на основі урахування численних зовнішніх та внутрішніх факторів, які здатні модифікувати фармакокінетику етанолу. Determination of blood alcohol concentration (ВАС) is necessary in many criminal cases. Retro-grade extrapolation and determination of the level of alcohol in the body at certain points before the sampling is possible only on the background of correct interpreting the data on the pharma-cokinetics of ethanol, its interaction with other medicinal drugs and narcotic substances. This led to the goal of the presented work: to analyze current published data regarding the pharmacoki-netics of ethanol, focusing on the points that are of practical importance for forensic medicine. In pharmacokinetics of orally taken alcohol, there are two phases: absorption (resorption) and elimination, according to other data - three phases, adding to the above mentioned phase of dif-fusion (distribution). The elimination of ethanol in mild or moderate intoxication is described by zero-order kinetics, in severe intoxication - by the 1st order kinetics. Until recently, ВАС calcu-lations for forensic purposes were carried out on the basis of simplified assumptions: linear pharmacokinetics of ethanol, constant elimination rate of ethanol in the full range of time, con-stant absorption rate and constant time of peak concentration in the blood, but simplified and idealized assumptions limit the possibility of retrograde extrapolation and raise the question of more advanced models of alcohol pharmacokinetics. It is shown that the real alcohol elimination curve differs from Widmark zero order kinetics and reflects the process of elimination like Michaelis-Menten model. Calculations for the specified model differ significantly from zero-order model to the side of higher concentration and longer duration the estimated time. For fo-rensic medicine, it is interesting to determine ethyl alcohol concentration not only in the blood but also in perspirated air (breath-alcohol concentration). The average rate of ethanol disappear-ance from the blood is close to the rate of its excretion with breath, but breath test results are lower than the corresponding ВАС that is necessary to take into account when determined con-centration is near the limit of minimum acceptable alcohol. Ethanol is excreted by skin and transdermal alcohol testing is suitable for prolonged non-invasive monitoring of drinking behav-ior. In forensic investigations, urine is often use to determine alcohol, and the ratio of ВАС and urine alcohol concentration is analyzed in the scientific literature. In urine, etylhglucuronid, ethanol metabolite, can be used as specific marker of «acute» alcohol consumption. Etylhglu-curonid and ethyl esters of fatty acids accumulate in the hair, and exceeding a certain level of these substances in the hair samples may indicate chronic alcohol abuse. Pharmacokinetics of ethanol depends on gender, age, со-administered medicines and food. The interaction of alcohol and medicinal drugs can alter metabolism of ethanol as well as the drugs, including antibiotics, antihistamines, barbiturates, benzodiazepines, H2-receptor blockers, analgesics, sedatives and herbal preparations. Medications that increase the basal metabolic rate, are able to increase the rate of alcohol oxidation. Pre-system metabolism and absorption of ethanol can be changed by the drugs that regulate the secretion and motility of the gastrointestinal tract. Thus, the main pro-visions of ethanol pharmacokinetics are the basis for forensic examination in cases related to al-cohol. Modern investigations are focused on numerous external and internal factors that can modify the pharmacokinetics of ethanol, which is aimed at the improvement of individualization and accuracy of diagnosis. Статья посвящена анализу литературных источников, касающихся фармакокинетики этанола с акцентированием внимания на тех моментах, которые имеют практическое значение для судебной медицины. Показано, что ретроградная экстраполяция и определение уровня алкоголя в организме на определенный момент времени до взятия образцов биоматериала проводится путем интерпретации данных про абсорбцию, распределение и элиминацию этанола, его взаимодействие с другими лекарственными средствами и наркоти-ческими веществами. В этих условиях повышение индивидуализации и точности диагностики возможно на основе учета многочисленных внешних и внутренних факторов, которые способны модифицировать фармакокинетику этанола.