vmireavizВестник медицинского института «РЕАВИЗ». Реабилитация, Врач и ЗдоровьеBulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH)2226-762X2782-1579РЕАВИЗ10.20340/vmi-rvz.2023.4.ICTM.1vmireaviz-772Research ArticleИнформационно-вычислительные технологии в медицинеInformation technology in medicineМатематическое моделирование распределения этанола в биологических жидкостях организмаMathematical modeling of ethanol distribution in body fluidshttps://orcid.org/0000-0002-7380-3766НедуговГ. В.NedugovG. V.

Недугов Герман Владимирович - доктор медицинских наук, заведующий кафедрой судебной медицины.

Ул. Чапаевская, д. 89, Самара, 443099

German V. Nedugov - Dr. Sci. (Med), Head of the Department of Forensic Medicine.

89 Chapaevskaya str., Samara, 443099

nedugovh@mail.ruСамарский государственный медицинский университетРоссияSamara State Medical UniversityRussian Federation202314092023134169174Copyright © Недугов Г.В., 20232023Недугов Г.В.Nedugov G.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik.reaviz.ru/jour/article/view/772

Цель исследования: построение кинетической модели распределения этанола в биологических жидкостях организма, а также её реализация в формате компьютерных программ. Выполнено аналитическое математическое моделирование кинетики этанола в жидких средах организма после однократного и многократного перорального приема алкоголя. Разработано уравнение распределения этанола во внутренних средах и иных жидкостях организма, основанное на кинетической модели элиминации нулевого порядка с абсорбцией и безвозвратным дефицитом абсорбции, а также достижением равновесного состояния с плазмой крови первого порядка. На базе указанной кинетической модели построены вычислительные алгоритмы оценки в жидкостях организма концентрации этанола в заданный момент времени, пиковой концентрации этанола и времени её достижения, времени полного выведения этанола, начала и окончания периода ложной элиминации. Получены решения задачи определения количества принятого этанола по его концентрации в биологической жидкости и уровня этанолемии в этот момент времени с возможностью расчёта их предельных абсолютных погрешностей. Построенная кинетическая модель обобщена на любое количество приемов этанола, разделенных временными промежутками любой продолжительности. Разработанные вычислительные алгоритмы реализованы в формате компьютерных программ «Alcohol Calculator V 7.0» и «Alcohol Calculator V 6.0», которые рекомендуется использовать при судебно-медицинской экспертной оценке острой алкогольной интоксикации.

The aim of the study is to build a kinetic model of ethanol distribution in biological body fluids, as well as its implementation in the format of computer programs. Analytical mathematical modeling of ethanol kinetics in body fluids after single and multiple oral alcohol intake was performed. An equation for the distribution of ethanol in internal media and other body fluids has been developed based on a kinetic model of zero-order elimination with absorption and irrevocable absorption deficiency, as well as achieving an equilibrium state with first-order blood plasma. On the basis of this kinetic model, computational algorithms are constructed for estimating the concentration of ethanol in body fluids at a given time, the peak concentration of ethanol and the time of its achievement, the time of complete removal of ethanol, the beginning and end of the false elimination period. Solutions to the problem of determining the amount of ethanol taken by its concentration in the biological fluid and the level of etholemia at this point in time with the possibility of calculating their maximum absolute errors are obtained. The constructed kinetic model is generalized to any number of ethanol receptions separated by time intervals of any duration. The developed computational algorithms are implemented in the format of the computer programs 'Alcohol Calculator V 7.0" and "Alcohol Calculator V 6.0", which are recommended for use in the forensic medical expert assessment of acute alcohol intoxication.

фармакокинетика этанолабиологическая жидкостьматематическое моделированиекинетическое уравнениекомпьютерная программаpharmacokinetics of ethanolbiological fluidmathematical modelingkinetic equationcomputer programИсследование проводилось без спонсорской поддержкиThis research received no external fundingReferencesKugelberg FC, Jones AW. Interpreting results of ethanol analysis in postmortem specimens: a review of the literature. Forensic Sci Int. 2007;165(1):10-29. https://doi.Org/10.1016/j.forsciint.2006.05.0041 Kugelberg FC, Jones AW. Interpreting results of ethanol analysis in postmortem specimens: a review of the literature. Forensic Sci Int. 2007;165(1):10-29. https://doi.Org/10.1016/j.forsciint.2006.05.004de Campos EG, da Costa BRB, Dos Santos FS, Monedeiro F, Alves MNR, Santos Junior WJR et al. Alternative matrices in forensic toxicology: a critical review. Forensic Toxicol. 2022;40(1):1-18. https://doi.org/10.1007/s11419-021-00596-52 de Campos EG, da Costa BRB, Dos Santos FS, Monedeiro F, Alves MNR, Santos Junior WJR et al. Alternative matrices in forensic toxicology: a critical review. Forensic Toxicol. 2022;40(1):1-18. https://doi.org/10.1007/s11419-021-00596-5Savini F, Tartaglia A, Coccia L, Palestini D, D'Ovidio C, de Grazia U et al. Ethanol Determination in Post-Mortem Samples: Correlation between Blood and Vitreous Humor Concentration. Molecules. 2020;25(11):2724. https://doi.org/10.3390/molecules251227243 Savini F, Tartaglia A, Coccia L, Palestini D, D'Ovidio C, de Grazia U et al. Ethanol Determination in Post-Mortem Samples: Correlation between Blood and Vitreous Humor Concentration. Molecules. 2020;25(11):2724. https://doi.org/10.3390/molecules25122724Hardin GG. Postmortem blood and vitreous humor ethanol concentrations in a victim of a fatal motor vehicle crash. J Forensic Sci. 2002;47(2):402-403.4 Hardin GG. Postmortem blood and vitreous humor ethanol concentrations in a victim of a fatal motor vehicle crash. J Forensic Sci. 2002;47(2):402-403.Chun HJ, Poklis JL, Poklis A, Wolf CE. Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector. J Anal Toxicol. 2016;40(7):653-658. https://doi.org/10.1093/jat/bkw0755 Chun HJ, Poklis JL, Poklis A, Wolf CE. Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector. J Anal Toxicol. 2016;40(7):653-658. https://doi.org/10.1093/jat/bkw075Moore KA, Kunsman GW, Levine BS, Herman MM, Cervenak J, Hyde TM. A comparison of ethanol concentrations in the occipital lobe and cerebellum. Forensic Sci Int. 1997;86(1-2):127-134. https://doi.Org/10.1016/s0379-0738(97)02129-46 Moore KA, Kunsman GW, Levine BS, Herman MM, Cervenak J, Hyde TM. A comparison of ethanol concentrations in the occipital lobe and cerebellum. Forensic Sci Int. 1997;86(1 -2):127-134. https://doi.Org/10.1016/s0379-0738(97)02129-4Garriott JC. Skeletal muscle as an alternative specimen for alcohol and drug analysis. J Forensic Sci. 1991 ;36(1 ):60-69.7 Garriott JC. Skeletal muscle as an alternative specimen for alcohol and drug analysis. J Forensic Sci. 1991 ;36(1 ):60-69.Ohshima T, Kondo T, Sato Y, Takayasu T. Postmortem alcohol analysis of the synovial fluid and its availability in medico-legal practices. Forensic Sci Int. 1997;90(1-2):131-138. https://doi.Org/10.1016/s0379-0738(97)00161-88 Ohshima T, Kondo T, Sato Y, Takayasu T. Postmortem alcohol analysis of the synovial fluid and its availability in medico-legal practices. Forensic Sci Int. 1997;90(1 -2):131 -138. https://doi.Org/10.1016/s0379-0738(97)00161 -8Buyuk Y, Eke M, Cagdir AS, Karaaslan HK. Post-mortem alcohol analysis in synovial fluid: an alternative method for estimation of blood alcohol level in medico-legal autopsies? Toxicol Mech Methods. 2009;19(5):375-378. https://doi.org/10.1080/153765109029712929 Buyuk Y, Eke M, Cagdir AS, Karaaslan HK. Post-mortem alcohol analysis in synovial fluid: an alternative method for estimation of blood alcohol level in medico-legal autopsies? Toxicol Mech Methods. 2009;19(5):375-378. https://doi.org/10.1080/15376510902971292Thelander G, Kugelberg FC, Jones AW. High Correlation between Ethanol Concentrations in Postmortem Femoral Blood and in Alternative Biological Specimens, but Large Uncertainty When the Linear Regression Model Was Used for Prediction in Individual Cases. J Anal Toxicol. 2020;44(5):415-421. https://doi.org/10.1093/jat/bkaa01810 Thelander G, Kugelberg FC, Jones AW. High Correlation between Ethanol Concentrations in Postmortem Femoral Blood and in Alternative Biological Specimens, but Large Uncertainty When the Linear Regression Model Was Used for Prediction in Individual Cases. J Anal Toxicol. 2020;44(5):415-421. https://doi.org/10.1093/jat/bkaa018Lin Z, Wang H, Jones AW, Wang F, Zhang Y, Rao Y. Evaluation and review of ways to differentiate sources of ethanol in postmortem blood. Int J Legal Med. 2020; 134(5):2081 -2093. https://doi.Org/10.1007/s00414-020-02415-911 Lin Z, Wang H, Jones AW, Wang F, Zhang Y, Rao Y. Evaluation and review of ways to differentiate sources of ethanol in postmortem blood. Int J Legal Med. 2020; 134(5):2081 -2093. https://doi.Org/10.1007/s00414-020-02415-9Wachholz P, Skowronek R, Pawlas N. Assessing the applicability of cerebrospinal fluid collected from the spinal cord for the determination of ethyl alcohol in post-mortem toxicology. Forensic Sci Med Pathol. 2023;19(1):44-49. https://doi.org/10.1007/s12024-022-00560-812 Wachholz P, Skowronek R, Pawlas N. Assessing the applicability of cerebrospinal fluid collected from the spinal cord for the determination of ethyl alcohol in post-mortem toxicology. Forensic Sci Med Pathol. 2023;19(1):44-49. https://doi.org/10.1007/s12024-022-00560-8Jones AW. Ethanol distribution ratios between urine and capillary blood in controlled experiments and in apprehended drinking drivers. J Forensic Sci. 1992;37(1):21-34.13 Jones AW. Ethanol distribution ratios between urine and capillary blood in controlled experiments and in apprehended drinking drivers. J Forensic Sci. 1992;37(1):21-34.Недугов ГВ. Математическое моделирование кинетики однократного приема этанола. Вестник медицинского института «РЕАВИЗ». Реабилитация, Врач и Здоровье. 2022; 12(5): 148-156. https://doi.Org/10.20340/vmi-rvz.2022.6.ICTM.1Nedugov GV. Mathematical modeling of the kinetics of a single intake of ethanol. Bulletin of the Medical Institute "Reaviz" (Rehabilitation, Doctor and Flealth). 2022; 12(5): 148156. (In Russ.) https://doi.Org/10.20340/vmi-rvz.2022.6.ICTM.1Недугов Г.В. Математическое моделирование кинетики многократного приёма этанола. Вестник медицинского института «РЕАВИЗ». Реабилитация, Врач и Здоровье. 2023; 13(1): 153-160. https://doi.Org/10.20340/vmi-rvz.2023.1.ICTM.2Nedugov GV. Mathematical modeling of the kinetics of multiple ethanol intake. Bulletin of the Medical Institute 'Reaviz" (Rehabilitation, Doctor and Flealth). 2023;13(1):153-160. (In Russ.) https://doi.Org/10.20340/vmi-rvz.2023.1.ICTM.2Zhu L, Pei W, Thiele I, Mahadevan R. Integration of a physiologically-based pharmacokinetic model with a whole-body, organ-resolved genome-scale model for characterization of ethanol and acetaldehyde metabolism. PLoS Comput Biol. 2021 ;17(7):e1009110. https://d0i.0rg/l0.1371/journal.pcbi.100911016 Zhu L, Pei W, Thiele I, Mahadevan R. Integration of a physiologically-based pharmacokinetic model with a whole-body, organ-resolved genome-scale model for characterization of ethanol and acetaldehyde metabolism. PLoS Comput Biol. 2021 ;17(7):e1009110. https://d0i.0rg/l0.1371/journal.pcbi.1009110Jenkins AJ, Levine BS, Smialek JE. Distribution of ethanol in postmortem liver. J Forensic Sci. 1995;40(4):611-613.17 Jenkins AJ, Levine BS, Smialek JE. Distribution of ethanol in postmortem liver. J Forensic Sci. 1995;40(4):611-613.

The authors declare that there are no conflicts of interest present.