mvistМедицина высоких технологийTitle3034-008X2949-550410.63769/3034-008X-2026-1-1-74-84mvist-7Research ArticleХИРУРГИЯSURGERYВлияние мини-гастрошунтирования на биодоступность пероральных полусинтетических пенициллинов: клинико-фармакологический анализOne-anastomosis gastric bypass and oral semisynthetic penicillins bioavailability: Clinical pharmacology analysishttps://orcid.org/0009-0003-2498-1771МироновК. Э.MironovK. E.

Константин Эдуардович Миронов

129128 Москва, ул. Будайская, 2

127473 Москва, ул. Делегатская, 20, стр. 1

Konstantin Eduardovich Mironov

2 Budayskaya St., Moscow 129128

20–1 Delegatskaya St., Moscow 127473

mironov-k@mail.ruhttps://orcid.org/0009-0009-0381-6092ВардаевЛ. И.VardaevL. I.

129128 Москва, ул. Будайская, 2

127473 Москва, ул. Делегатская, 20, стр. 1

2 Budayskaya St., Moscow 129128

20–1 Delegatskaya St., Moscow 127473

https://orcid.org/0009-0009-5057-8031ТереховаА. О.TerekhovaA. O.

29128 Москва, ул. Будайская, 2

119017 Москва, Малый Толмачевский пер., 8 / 11, стр. 3

2 Budayskaya St., Moscow 129128

Bld. 3, 8 / 11 Tolmachevsky Lane, Moscow 119017

https://orcid.org/0000-0002-8092-0573ЛуцевичО. Э.LutsevichO. E.

129128 Москва, ул. Будайская, 2

111123 Москва, ш. Энтузиастов, 62

2 Budayskaya St., Moscow 129128

62 Entuziastov Road, Moscow 111123

ЧУЗ «Центральная клиническая больница “РЖД-Медицина”»; ФГБОУ ВО «Российский университет медицины» Минздрава РоссииРоссияCentral Clinical Hospital “Russian Railways Medicine”; Russian University of Medicine, Ministry of Health of RussiaRussian FederationЧУЗ «Центральная клиническая больница “РЖД-Медицина”»; Медицинский центр MedSwissРоссияCentral Clinical Hospital “Russian Railways Medicine”; MedSwiss Medical CenterRussian FederationЧУЗ «Центральная клиническая больница “РЖД-Медицина”»; АО «Центр эндохирургии и литотрипсии»РоссияCentral Clinical Hospital “Russian Railways Medicine”; Center of Endosurgery and LithotripsyRussian Federation202615102026117484Copyright © Миронов К.Э., Вардаев Л.И., Терехова А.О., Луцевич О.Э., 20262026Миронов К.Э., Вардаев Л.И., Терехова А.О., Луцевич О.Э.Mironov K.E., Vardaev L.I., Terekhova A.O., Lutsevich O.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htmed-j.com/jour/article/view/7Введение

Введение. Мини-гастрошунтирование (МГШ) относится к шунтирующим бариатрическим операциям, которые изменяют анатомию верхних отделов желудочно-кишечного тракта. У оперированных пациентов пищевой комок минует двенадцатиперстную кишку и проксимальный отдел тощей кишки, что может влиять на всасывание пероральных лекарственных препаратов, включая полусинтетические пенициллины.

Цель исследования – оценить влияние МГШ на биодоступность пероральных полусинтетических пенициллинов и определить клинико-фармакологические подходы к их применению после бариатрических вмешательств данного типа.

Материалы и методы

Материалы и методы. Проведен обзор и клинико-фармакологический анализ публикаций, посвященных анатомо-физиологическим изменениям после бариатрических операций, механизмам кишечной абсорбции амоксициллина, ампициллина, амоксициллина с клавулановой кислотой и пенициллиназоустойчивых изоксазолилпенициллинов, прежде всего оксациллина, а также фармакокинетике пероральных антибиотиков после шунтирующих вмешательств. Выполнен поиск научных источников в международных и российских базах, включая PubMed, Cochrane Library, Google Scholar, Crossref, eLibrary.ru и CyberLeninka, а также на сайтах научных журналов и издательств. Дополнительно анализировались публикации с проверяемыми цифровыми идентификаторами и российские статьи по бариатрической хирургии.

Результаты

Результаты. Клинических исследований фармакокинетики пероральных полусинтетических пенициллинов именно после МГШ в доступной литературе не выявлено. Основные данные получены в исследованиях гастрошунтирования по Ру; они свидетельствуют о непредсказуемости системной экспозиции амоксициллина, особенно при использовании твердых лекарственных форм. Потенциально на фармакокинетику влияют выключение проксимальной части тонкой кишки, изменение кислотности желудочного резервуара, ускорение кишечного транзита, лекарственная форма, наличие гипоальбуминемии и признаков гипосорбции.

Заключение

Заключение. Пероральные пенициллины после МГШ не следует считать заведомо неэффективными. Однако их применение требует учета тяжести инфекции, лекарственной формы, сохранности перорального приема и оценки раннего клинического ответа. При тяжелой инфекции, системных проявлениях воспаления или признаках ненадежной пероральной экспозиции предпочтителен парентеральный путь введения.

Introduction

Introduction. One-anastomosis gastric bypass (OAGB) is a bypass bariatric procedure that combines restrictive and malabsorptive components and is associated with anatomical changes in the upper gastrointestinal tract. After this operation, the food stream bypasses the duodenum and the proximal jejunum, which may affect the absorption of oral medications, including semisynthetic penicillins.

Objective

Objective. To assess the potential effect of OAGB on the bioavailability of oral semisynthetic penicillins and to define clinical pharmacology approaches to their use in patients after this type of bypass bariatric procedure.

Materials and methods

Materials and methods. A review and clinical pharmacology analysis of published data were performed. The search included studies on anatomical and physiological changes after bariatric surgery, mechanisms of intestinal absorption of amoxicillin, ampicillin, amoxicillin with clavulanic acid, and penicillinase-resistant isoxazolyl penicillins, primarily oxacillin, as well as studies on the pharmacokinetics of oral antibiotics after bypass bariatric procedures. The literature search was conducted in international and Russian scientific databases, including PubMed, Cochrane Library, Google Scholar, Crossref, eLibrary.ru, and CyberLeninka, as well as on the websites of scientific journals and publishers. Publications with verifiable digital object identifiers and Russian sources on bariatric surgery were additionally analyzed.

Results and discussion

Results and discussion. No direct clinical pharmacokinetic studies of oral semisynthetic penicillins specifically after one-anastomosis gastric bypass were identified in the available literature. Most evidence comes from studies after Roux-en-Y gastric bypass and suggests that systemic exposure to amoxicillin may be unpredictable, especially when solid dosage forms are used. Potentially relevant factors include exclusion of the proximal small intestine, changes in gastric pouch acidity, accelerated intestinal transit, dosage form, hypoalbuminemia, and signs of malabsorption.

Conclusion

Conclusion. Oral penicillins after OAGB should not be considered inherently ineffective. However, their use requires assessment of infection severity, dosage form, preserved oral intake, and early clinical response. In severe infection, systemic inflammatory manifestations, or signs of unreliable oral exposure, parenteral administration is preferable.

мини-гастрошунтированиегастрошунтирование с одним анастомозомбариатрическая хирургияамоксициллинамоксициллин с клавулановой кислотойполусинтетические пенициллиныбиодоступностьфармакокинетикалекарственная абсорбцияone-anastomosis gastric bypassbariatric surgeryamoxicillinamoxicillin clavulanatesemisynthetic penicillinsbioavailabilitypharmacokineticsdrug absorptionReferencesНеймарк А.Е., Яшков Ю.И., Хациев Б.Б. и др. Результаты первой Всероссийской консенсус-конференции по бариатрической хирургии. Хирургия. Журнал им. Н.И. Пирогова 2024;(3):87–94. DOI: 10.17116/hirurgia202403187Neimark A.E., Yashkov Yu.I., Khatsiev B.B. et al. Results of the first All-Russian consensus conference on bariatric surgery. Khirurgiya. Zhurnal im. N.I. Pirogova = Pirogov Russian Journal of Surgery 2024;(3):87–94. DOI: 10.17116/hirurgia202403187. (In Russ.)De Luca M., Piatto G., Merola G. et al. IFSO Update position statement on one anastomosis gastric bypass (OAGB). Obes Surg 2021;31(7):3251–78. DOI: 10.1007/s11695-021-05413-xDe Luca M., Piatto G., Merola G. et al. IFSO Update position statement on one anastomosis gastric bypass (OAGB). Obes Surg 2021;31(7):3251–78. DOI: 10.1007/s11695-021-05413-xYashkov Y.I., Kuzin N.M., Sedletsky Y.I. Obesity surgery in Russia. Obes Surg 1999;9:40–3. DOI: 10.1381/096089299765553737Yashkov Y.I., Kuzin N.M., Sedletsky Y.I. Obesity surgery in Russia. Obes Surg 1999;9:40–3. DOI: 10.1381/096089299765553737Дедов И.И., Мокрышева Н.Г., Мельниченко Г.А. и др. Клинические рекомендации «Ожирение» Минздрава России. Версия 2024 года. Вестник репродуктивного здоровья 2025;4(2):14–30. DOI: 10.14341/brh12763Dedov I.I., Mokrysheva N.G., Melnichenko G.A. et al. Clinical recommendations “Diabetes mellitus” of the Russian Ministry of Health. Version of the year 2024. Vestnik reproduktivnogo zdorovya = Bulletin of Reproductive Health 2025;4(2):14–30. DOI: 10.14341/brh12763. (In Russ.)Barr W.H., Zola E.M., Candler E.L. et al. Differential absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther 1994;56(3):279–85. DOI: 10.1038/clpt.1994.138Barr W.H., Zola E.M., Candler E.L. et al. Differential absorption of amoxicillin from the human small and large intestine. Clin Pharmacol Ther 1994;56(3):279–85. DOI: 10.1038/clpt.1994.138Bretschneider B., Brandsch M., Neubert R. Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res 1999;16(1):55–61. DOI: 10.1023/A:1018814627484Bretschneider B., Brandsch M., Neubert R. Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res 1999;16(1):55–61. DOI: 10.1023/A:1018814627484Sala-Rabanal M., Loo D.D.F., Hirayama B.A., Wright E.M. Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2. Am J Physiol Renal Physiol 2008;294(6):F1422–32. DOI: 10.1152/ajprenal.00030.2008Sala-Rabanal M., Loo D.D.F., Hirayama B.A., Wright E.M. Molecular mechanism of dipeptide and drug transport by the human renal H+/oligopeptide cotransporter hPEPT2. Am J Physiol Renal Physiol 2008;294(6):F1422–32. DOI: 10.1152/ajprenal.00030.2008Fujiwara K., Shin M., Miyazaki T., Maruta Y. Immunocytochemistry for amoxicillin and its use for studying uptake of the drug in the intestine, liver, and kidney of rats. Antimicrob Agents Chemother 2011;55(1):62–71. DOI: 10.1128/AAC.01031-10Fujiwara K., Shin M., Miyazaki T., Maruta Y. Immunocytochemistry for amoxicillin and its use for studying uptake of the drug in the intestine, liver, and kidney of rats. Antimicrob Agents Chemother 2011;55(1):62–71. DOI: 10.1128/AAC.01031-10Eshelman F.N., Spyker D.A. Pharmacokinetics of amoxicillin and ampicillin: crossover study of the effect of food. Antimicrob Agents Chemother 1978;14(4):539–43. DOI: 10.1128/AAC.14.4.539Eshelman F.N., Spyker D.A. Pharmacokinetics of amoxicillin and ampicillin: crossover study of the effect of food. Antimicrob Agents Chemother 1978;14(4):539–43. DOI: 10.1128/AAC.14.4.539Xu S.-M., Qin F., Zhang Y.-D., Xu P.-S. Pharmacokinetics of amoxicillin and clavulanate potassium for suspension 200 mg/28.5 mg in healthy subjects: sample add stabilizer study and food effects. Clin Pharmacol Drug Dev 2022;11(11):1314–21. DOI: 10.1002/cpdd.1143Xu S.-M., Qin F., Zhang Y.-D., Xu P.-S. Pharmacokinetics of amoxicillin and clavulanate potassium for suspension 200 mg/28.5 mg in healthy subjects: sample add stabilizer study and food effects. Clin Pharmacol Drug Dev 2022;11(11):1314–21. DOI: 10.1002/cpdd.1143Wu G., Zheng Y., Zhou H. et al. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses. Drug Des Devel Ther 2015;9:5687–95. DOI: 10.2147/DDDT.S92117Wu G., Zheng Y., Zhou H. et al. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses. Drug Des Devel Ther 2015;9:5687–95. DOI: 10.2147/DDDT.S92117Rocha M.B.S., De Nucci G., Lemos F.N. et al. Impact of bariatric surgery on the pharmacokinetics parameters of amoxicillin. Obes Surg 2019;29(3):917–27. DOI: 10.1007/s11695-018-3591-3Rocha M.B.S., De Nucci G., Lemos F.N. et al. Impact of bariatric surgery on the pharmacokinetics parameters of amoxicillin. Obes Surg 2019;29(3):917–27. DOI: 10.1007/s11695-018-3591-3Montanha M.C., Dos Santos Magon T.F., de Souza Alcantara C. et al. Reduced bioavailability of oral amoxicillin tablets compared to suspensions in Roux-en-Y gastric bypass bariatric subjects. Br J Clin Pharmacol 2019;85(9):2118–25. DOI: 10.1111/bcp.14023Montanha M.C., Dos Santos Magon T.F., de Souza Alcantara C. et al. Reduced bioavailability of oral amoxicillin tablets compared to suspensions in Roux-en-Y gastric bypass bariatric subjects. Br J Clin Pharmacol 2019;85(9):2118–25. DOI: 10.1111/bcp.14023Montanha M.C., Diniz A., Silva N.M.E.N. et al. Physiologically-based pharmacokinetic model on the oral drug absorption in Roux-en-Y gastric bypass bariatric patients: Amoxicillin tablet and suspension. Mol Pharm 2019;16(12):5025–34. DOI: 10.1021/acs.molpharmaceut.9b00870Montanha M.C., Diniz A., Silva N.M.E.N. et al. Physiologically-based pharmacokinetic model on the oral drug absorption in Roux-en-Y gastric bypass bariatric patients: Amoxicillin tablet and suspension. Mol Pharm 2019;16(12):5025–34. DOI: 10.1021/acs.molpharmaceut.9b00870Dalla Rosa G.M.L.L., Yamamoto P.A., Melo M.M.C. et al. Optimal dosing of amoxicillin in obese and post-gastric bypass patients using a population pharmacokinetics-pharmacodynamics model approach. J Antimicrob Chemother 2025;80(7):1893–901. DOI: 10.1093/jac/dkaf144Dalla Rosa G.M.L.L., Yamamoto P.A., Melo M.M.C. et al. Optimal dosing of amoxicillin in obese and post-gastric bypass patients using a population pharmacokinetics-pharmacodynamics model approach. J Antimicrob Chemother 2025;80(7):1893–901. DOI: 10.1093/jac/dkaf144Kingma J.S., Burgers D.M.T., Monpellier V.M. et al. Oral drug dosing following bariatric surgery: General concepts and specific dosing advice. Br J Clin Pharmacol 2021;87(12):4560–76. DOI: 10.1111/bcp.14913Kingma J.S., Burgers D.M.T., Monpellier V.M. et al. Oral drug dosing following bariatric surgery: General concepts and specific dosing advice. Br J Clin Pharmacol 2021;87(12):4560–76. DOI: 10.1111/bcp.14913Porat D., Vaynshtein J., Gibori R. et al. Stomach pH before vs. after different bariatric surgery procedures: Clinical implications for drug delivery. Eur J Pharm Biopharm 2021;160:152–7. DOI: 10.1016/j.ejpb.2021.01.016Porat D., Vaynshtein J., Gibori R. et al. Stomach pH before vs. after different bariatric surgery procedures: Clinical implications for drug delivery. Eur J Pharm Biopharm 2021;160:152–7. DOI: 10.1016/j.ejpb.2021.01.016Anvari S., Lee Y., Lam M. et al. The effect of bariatric surgery on oral antibiotic absorption: A systematic review. Obes Surg 2020;30(8):2883–92. DOI: 10.1007/s11695-020-04623-zAnvari S., Lee Y., Lam M. et al. The effect of bariatric surgery on oral antibiotic absorption: A systematic review. Obes Surg 2020;30(8):2883–92. DOI: 10.1007/s11695-020-04623-zPadwal R., Brocks D., Sharma A.M. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev 2010;11(1):41–50. DOI: 10.1111/j.1467-789X.2009.00614.xPadwal R., Brocks D., Sharma A.M. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev 2010;11(1):41–50. DOI: 10.1111/j.1467-789X.2009.00614.xBandlamudi N., Holt G., Graham Y. et al. Malnutrition following one-anastomosis gastric bypass: A systematic review. Obes Surg 2023;33(12):4137–46. DOI: 10.1007/s11695-023-06907-6Bandlamudi N., Holt G., Graham Y. et al. Malnutrition following one-anastomosis gastric bypass: A systematic review. Obes Surg 2023;33(12):4137–46. DOI: 10.1007/s11695-023-06907-6Bertrand T., Rives-Lange C., Jannot A.S. et al. 150-cm versus 200-cm biliopancreatic limb one-anastomosis gastric bypass: propensity score-matched analysis Obes Surg 2022;32(9):2839–45. DOI: 10.1007/s11695-022-06203-9Bertrand T., Rives-Lange C., Jannot A.S. et al. 150-cm versus 200-cm biliopancreatic limb one-anastomosis gastric bypass: propensity score-matched analysis Obes Surg 2022;32(9):2839–45. DOI: 10.1007/s11695-022-06203-9Robert M., Espalieu P., Pelascini E. et al. Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for obesity (YOMEGA): A multicentre, randomised, open-label, non-inferiority trial. Lancet 2019;393(10178):1299–309. DOI: 10.1016/S0140-6736(19)30475-1Robert M., Espalieu P., Pelascini E. et al. Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for obesity (YOMEGA): A multicentre, randomised, open-label, non-inferiority trial. Lancet 2019;393(10178):1299–309. DOI: 10.1016/S0140-6736(19)30475-1Keleidari B., Mahmoudieh M., Shahabi S. et al. Reversing one-anastomosis gastric bypass surgery due to severe and refractory hypoalbuminemia. World J Surg 2020;44(4):1200–8. DOI: 10.1007/s00268-019-05290-7Keleidari B., Mahmoudieh M., Shahabi S. et al. Reversing one-anastomosis gastric bypass surgery due to severe and refractory hypoalbuminemia. World J Surg 2020;44(4):1200–8. DOI: 10.1007/s00268-019-05290-7Wiesner A., Zagrodzki P., Paśko P. Do dietary interventions exert clinically important effects on the bioavailability of β-lactam antibiotics? A systematic review with meta-analyses. J Antimicrob Chemother 2024;79(4):722–57. DOI: 10.1093/jac/dkae028Wiesner A., Zagrodzki P., Paśko P. Do dietary interventions exert clinically important effects on the bioavailability of β-lactam antibiotics? A systematic review with meta-analyses. J Antimicrob Chemother 2024;79(4):722–57. DOI: 10.1093/jac/dkae028Roberts J.A., Abdul-Aziz M.H., Lipman J. et al. Individualised antibiotic dosing for patients who are critically ill: Challenges and potential solutions. Lancet Infect Dis 2014;14(6):498–509. DOI: 10.1016/S1473-3099(14)70036-2Roberts J.A., Abdul-Aziz M.H., Lipman J. et al. Individualised antibiotic dosing for patients who are critically ill: Challenges and potential solutions. Lancet Infect Dis 2014;14(6):498–509. DOI: 10.1016/S1473-3099(14)70036-2Оксациллин (Oxacillin): описание активного вещества. URL: https://www.vidal.ru/drugs/oxacillin__15756.Oxacillin: description of the active substance. URL: https://www.vidal.ru/drugs/oxacillin__15756. (In Russ.)

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