scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agencyscbmt-117Research ArticleРЕЛЕВАНТНОЕ И АЛЬТЕРНАТИВНОЕ БИОМОДЕЛИРОВАНИЕRELEVANT AND ALTERNATIVE BIOMODELLINGМатематическое моделирование параметров фармакокинетики ванкомицина: возможности и сравнение с результатами терапевтического лекарственного мониторингаMathematical modeling of vancomomycin pharmacokinetics parameters: opportunities and comparison with the results of therapeutic drug monitoringРаменскаяГ. В.RamenskayaG. V.noemail@neicon.ruШохинИ. Е.ShokhinI. E.noemail@neicon.ruЛукинаМ. В.LukinaM. V.mari-luk2010@yandex.ruАндрущишинаТ. Б.AndrushchyshinaT. B.noemail@neicon.ruЧукинаМ. А.ChukinaM. A.noemail@neicon.ruЦаревИ. Л.TsarevI. L.noemail@neicon.ruВартановаО. А.VartanovaO. A.noemail@neicon.ruМорозоваТ. Е.MorozovaT. E.noemail@neicon.ruФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)Russian Federation201826022019045162Copyright © Раменская Г.В., Шохин И.Е., Лукина М.В., Андрущишина Т.Б., Чукина М.А., Царев И.Л., Вартанова О.А., Морозова Т.Е., 20192019Раменская Г.В., Шохин И.Е., Лукина М.В., Андрущишина Т.Б., Чукина М.А., Царев И.Л., Вартанова О.А., Морозова Т.Е.Ramenskaya G.V., Shokhin I.E., Lukina M.V., Andrushchyshina T.B., Chukina M.A., Tsarev I.L., Vartanova O.A., Morozova T.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/117

Цель проспективного обсервационного исследования - сопоставить фармакокинетические параметры ванкомицина, полученные методом терапевтического лекарственного мониторинга и методом математического моделирования у пациентов хирургического профиля с нарушениями функции почек. Обследован 61 пациент (мужчины - 47 чел., женщины - 14) в возрасте 60,59±12,23 лет. Участники исследования разделены на две группы: первая - с острым почечным повреждением (66,6%), вторая - без него (33,4%). Равновесные остаточные и пиковые концентрации ванкомицина определяли методом высокоэффективной жидкостной хроматографии. Установлено, что значения равновесных остаточных концентраций ванкомицина через 48 ч от начала терапии достоверно ниже значений, полученных при математическом моделировании в группе пациентов с острым почечным повреждением (р=0,004). Значения равновесных остаточных концентраций на момент завершения терапии ванкомицином в группах с острым почечным повреждением (р=0,092) и без него (р=0,087) достоверно не отличаются. Фактические значения площади под фармакокинетической кривой за 24 ч были достоверно выше расчетного уровня в группах с острым почечным повреждением (р=0,011) и близки к достоверным в группе без него (р=0,056). При достижении равновесных остаточных концентраций на уровне 10-15 мкг/мл отношение площади под фармакокинетической кривой за 24 ч к минимальной подавляющей концентрации достигает целевых значений (более 400 мкг*ч/мл) через 48 ч от начала терапии и на момент завершения антибактериальной терапии. Различия фактических значений параметров фармакокинетики и полученных методом математического моделирования свидетельствуют о необходимости обязательного применения терапевтического лекарственного мониторинга у пациентов с нарушениями функции почек.

The purpose of a prospective observational study is to compare the pharmacokinetic parameters of vancomycin, obtained by therapeutic drug monitoring and mathematical modeling of surgical patients with renal dysfunction. A total of 61 patients (men - 47 people, women - 14) aged 60.59 ± 12.23 years were examined. The study participants were divided into two groups: the first with acute renal damage (66.6%), the second without it (33.4%). Equilibrium residual and peak concentrations of vancomycin were determined by high performance liquid chromatography. It was established that the values of the equilibrium residual concentrations of vancomycin after 48 hours from the start of therapy were significantly lower than the values obtained by mathematical modeling in the group of patients with acute renal damage (p=0.004). The values of the equilibrium residual concentrations at the time of completion of vancomycin therapy in groups with acute renal damage (p=0.092) and without it (p=0.087) do not differ significantly. The actual values of the area under the pharmacokinetic curve for 24 hours were significantly higher than the calculated level in the groups with acute renal damage (p=0.011) and close to reliable in the group without it (p=0.056). When equilibrium residual concentrations of 10-15 µg/ml are reached, the ratio of the area under the pharmacokinetic curve for 24 hours to the minimum inhibitory concentration reaches target values (more than 400 µg*h/ml) after 48 hours from the start of therapy and at the time of completion of antibiotic therapy. Differences in the actual values of pharmacokinetic parameters and those obtained by the method of mathematical modeling indicate the need for mandatory use of therapeutic drug monitoring in patients with renal dysfunction.

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A language and environment for statistical computing. Foundation for Statistical Computing, Vienna, Austria. 2017.Core T. A language and environment for statistical computing. Foundation for Statistical Computing, Vienna, Austria. 2017.DeRyke C.A., Alexander D.P. Optimizing Vancomycin Dosing Through Pharmacodynamic Assessment Targeting Area Under the Concentration-Time Curve/Minimum Inhibitory Concentration. Hospital Pharmacy, 44(9): 751-765.DeRyke C.A., Alexander D.P. Optimizing Vancomycin Dosing Through Pharmacodynamic Assessment Targeting Area Under the Concentration-Time Curve/Minimum Inhibitory Concentration. Hospital Pharmacy, 44(9): 751-765.Eyob D.A., Herald M., Koura F. Pharmacokinetics of Vancomycin in Extremely Obese Patients with Suspected or Confirmed Staphylococcus aureus Infections. PHARMACOTHERAPY. 2015. V. 35, No. 2. Pp. 127-139.Eyob D.A., Herald M., Koura F. 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Intensive Care Med., 2007; 33: 279-285.del Mar Fernández de Gatta Garcia M., Revilla N., Calvo M.-V., Domínguez-Gil A., Navarro A.S. Pharmacokinetic / pharmacodynamic analysis of vancomycin in ICU patients. Intensive Care Med., 2007; 33: 279-285.Matzke G.R., McGory R.W., Halstenson C.E., Keane W.F. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984; 25(4): 433-437.Matzke G.R., McGory R.W., Halstenson C.E., Keane W.F. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984; 25(4): 433-437.Moise-Broder P.A., Forrest A., Birmingham M.C., et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin. Pharmacokinet., 2004; 43: 925-942.Moise-Broder P.A., Forrest A., Birmingham M.C., et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin. Pharmacokinet., 2004; 43: 925-942.Murphy J.E., Gillespie D.E., Bateman C.V. Predictability of vancomycin trough concentrations using seven approaches for estimating pharmacokinetic parameters. Am. J. Health Syst. Pharm., 2006; 63: 2365-70.Murphy J.E., Gillespie D.E., Bateman C.V. Predictability of vancomycin trough concentrations using seven approaches for estimating pharmacokinetic parameters. Am. J. Health Syst. Pharm., 2006; 63: 2365-70.Neely M.N., Youn G., Jones B., Jelliffe R.W., Drusano G.L., Rodvold K.A., et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother., 2014; 58(1): 309-316.Neely M.N., Youn G., Jones B., Jelliffe R.W., Drusano G.L., Rodvold K.A., et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother., 2014; 58(1): 309-316.Pai M.P., Neely M., Rodvold K.A., Lodise T.P. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Advanced drug delivery reviews, 2014; 77: 50-57.Pai M.P., Neely M., Rodvold K.A., Lodise T.P. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Advanced drug delivery reviews, 2014; 77: 50-57.Patel N., Pai M.P., Rodvold K.A., Lomaestro В., Drusano G.L., Lodise T.P. Vancomycin: we can't get there from here. Clinical infectious diseases, 2011; 52(8): 969-974.Patel N., Pai M.P., Rodvold K.A., Lomaestro В., Drusano G.L., Lodise T.P. Vancomycin: we can't get there from here. Clinical infectious diseases, 2011; 52(8): 969-974.Prybylski J.P. Vancomycin trough concentration as a predictor of clinical outcomes in patients with Staphylococcus aureus bacteremia: a meta-analysis of observational studies. Pharmacotherapy: J. of Human Pharmacology and Drug Therapy, 2015; 35(10): 889-898.Prybylski J.P. Vancomycin trough concentration as a predictor of clinical outcomes in patients with Staphylococcus aureus bacteremia: a meta-analysis of observational studies. Pharmacotherapy: J. of Human Pharmacology and Drug Therapy, 2015; 35(10): 889-898.Rybak M., et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am. J. of Health-System Pharmacy, 2009; 66(1): 82-98.Rybak M., et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am. J. of Health-System Pharmacy, 2009; 66(1): 82-98.

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