Efficacy and safety of the drug Phosphogliv® URSO in patients with indications for oral litholysis: cholelithiasis and the pre-stone stage of the disease

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Abstract

Objective: To assess the efficacy and safety of an original combination of ursodeoxycholic acid (UDCA) and glycyrrhizic acid as an oral litholytic agent in routine clinical practice in patients with gallstone disease and other forms of cholelithiasis (e.g. biliary sludge).

Materials and methods: A multicenter retrospective study, with the collection and evaluation of data on the efficacy and safety of a UDCA – glycyrrhizinic acid combination, included 3,346 patients with indications for litholytic therapy who received the drug at an average daily dose of 10 mg/kg for 3 months. Efficacy was assessed based on ultrasound data, laboratory indicators, and severity of key clinical symptoms. Safety and tolerability were evaluated based on the frequency and severity of adverse events.

Results: By the end of treatment with the UDCA – glycyrrhizinic acid combination, 86% of patients with sludge and microcrystals showed a statistically significant positive change in ultrasound imaging, with their complete regression (p<0.0001). Among patients with small cholesterol stones, 47% exhibited reduced gallbladder wall thickness and 42% showed a decrease in gallbladder size (p<0.0001). After 3 months of treatment, all patients demonstrated a significant reduction in serum alkaline phosphatase and total cholesterol levels (p<0.0001). Additionally, 99.5% of patients reported a reduction or complete disappearance of biliary dyspepsia symptoms. Adverse events were reported in 6% of cases, mainly as transient dyspeptic disorders.

Conclusion: The original UDCA – glycyrrhizinic acid combination demonstrated clinical efficacy in patients with indications for oral litholysis by reducing bile lithogenicity, particularly in early stages of gallstone disease. The treatment promoted regression of biliary sludge and dissolution of microliths, improved ultrasound parameters, and exerted anti-inflammatory and hypocholesterolemic effects, with a favorable safety profile.

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About the authors

I. G. Nikitin

Pirogov Russian National Research Medical University

Author for correspondence.
Email: igor.nikitin.64@mail.ru
ORCID iD: 0000-0003-1699-0881

Dr. Sci. (Med.), Professor, Head of the Department of Hospital therapy named after Academician G.I. Storozhakov

Russian Federation, Moscow

A. B. Danilov

Institute of Interdisciplinary Medicine; I.M. Sechenov First Moscow State Medical University

Email: danilov@intermeda.ru
ORCID iD: 0000-0001-8904-2538

Dr. Sci. (Med.), Head of the Department of Nervous Diseases, Institute of Professional Education

Russian Federation, Moscow; Moscow

A. A. Poromov

Mechnikov Research Institute for Vaccines and Sera; Patrice Lumumba Peoples Friendship University of Russia

Email: poromov-aa@rudn.ru
ORCID iD: 0000-0002-2004-3935

Cand. Sci. (Biol.), Associate Professor

Russian Federation, Moscow; Moscow

T. N. Yankovaya

Smolensk State Medical University

Email: yankovaya-tn@yandex.ru

Cand. Sci (Med.) Associate Professor

Russian Federation, Smolensk

I. D. Rybnikova

Multidisciplinary Medical Center «Expert Clinic»

Email: irarib84@mail.ru

Therapist

Russian Federation, Smolensk

O. V. Mikhailova

Kuzbass Regional Clinical Hospital named after S.V. Belyaev

Email: olgavladmix@mail.ru

Gastroenterologist

Russian Federation, Kemerovo

N. O. Chuprakova

City Clinical Polyclinic No.4, Perm

Email: marina159.59@mail.ru

Gastroenterologist

Russian Federation, Perm

A. P. Kudryavtseva

Municipal Healthcare Institution «City Polyclinic No. 19», Kazan

Email: kud.a72@mail.ru

Therapist

Russian Federation, Kazan

O. V. Yunusova

State Autonomous Budgetary Institution Zelenodolsk Central Regional Hospital

Email: igor.nikitin.64@mail.ru

Osinovskaya Multidisciplinary Polyclinic, Therapist

Russian Federation, Republic of Tatarstan, Zelenodolsk district, Osinovskoye rural settlement, Osinovo village

N. V. Makarova

Medical and Diagnostic Center «BIOMED»

Email: habiba1982@bk.ru

Gastroenterologist

Russian Federation, Kazan

L. R. Shavalieva

Medical Consultative and Diagnostic Center №7 «Aibolit»

Email: leilaax@rambler.ru

Gastroenterologist

Russian Federation, Kazan

L. I. Demidova

State Autonomous Budgetary Institution Zelenodolsk Central Regional Hospital

Email: demidova8@bk.ru

Osinovskaya Multidisciplinary Polyclinic, Therapist

Russian Federation, Republic of Tatarstan, Zelenodolsk district, Osinovskoye rural settlement, Osinovo village

V. I. Kozlov

Clinic of Individual Medicine «G Clinic Genesis Group»

Email: equilibrium92@yandex.ru

Gastroenterologist

Russian Federation, Kazan

F. M. Karimullina

City Clinical Hospital of the Russian Railways «Medicine»

Email: fatimakarimullina@yandex.ru

Polyclinic №1, Therapist

Russian Federation, Kazan

Z. R. Fazylova

Multidisciplinary Clinic «SITIDOK-expert»

Email: zilya87@inbox.ru

Gastroenterologist

Russian Federation, Kazan

References

  1. Ивашкин В.Т., Маев И.В., Баранская Е.К. и др. Рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению желчнокаменной болезни. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016;26(3):64–80. [Ivashkin V.T., Mayev I.V., Baranskaya Ye.K., et al. Gallstone disease diagnosis and treatment: guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;26(3):64–80. (In Russ.)]. https://doi.org/10.22416/1382-4376-2016-26-3-64-80
  2. Литовский И.А., Гордиенко А.В. Желчнокаменная болезнь, холециститы и некоторые ассоциированные с ними заболевания (вопросы патогенеза, диагностики, лечения). Санкт-Петербург, 2019. 358 с. [Litovsky I.A., Gordienko A.V. Gallstone disease, cholecystitis and some associated diseases (pathogenesis, diagnostics, treatment). St. Petersburg, 2019. 358 p. (In Russ.)].
  3. Тарасенко С.В., Зайцев О.В., Тюленев Д.О. и др. Распространенность осложненных форм желчнокаменной болезни. Наука молодых (ERUDITIO JUVENIUM). 2018;6(2):218–24. [Tarasenko S.V., Zaitsev O.V., Tyulenev D.O., et al. Incidence of complicated forms of cholelithiasis. Science of the young (Eruditio Juvenium). 2018;6(2):218–24. (In Russ.)]. https://doi.org/10.23888/HMJ201862218-224.
  4. Ревишвили А.Ш., Оловянный В.Е., Гогия Б.Ш. и др. Хирургическая помощь в Российской Федерации. М., 2024. 192 с. [Revishvili A.Sh., Olovyanny V.E., Gogia B.Sh. et al. Surgical care in the Russian Federation. M., 2024. 192 p. (In Russ.)].
  5. Hall L., Halle-Smith J., Evans R., et al. Ursodeoxycholic acid in the management of symptomatic gallstone disease: systematic review and clinician survey. BJS Open. 2023;7(2):zrac152. https://doi.org/10.1093/bjsopen/zrac152
  6. Jaruvongvanich V., Sanguankeo A., Upala S. Significant Association Between Gallstone Disease and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2016;61(8):2389–96. https://doi.org/10.1007/s10620-016-4125-2
  7. Вахрушев Я.М., Косарева Т.С., Сучкова Е.В. и др. Биохимические и структурные изменения желчи при неалкогольной жировой болезни печени. Экспериментальная и клиническая гастроэнтерология. 2024;223(3):57–64. [Vakhrushev Ya.M., Kosareva T.S., Suchkova E.V., et al. Biochemical and structural changes in bile in non-alcoholic fatty liver disease. Eksperimental’naya i klinicheskaya gastroenterologiya=Experimental and Clinical Gastroenterology. 2024;223(3):57–64. (In Russ.)]. https://doi.org/10.31146/1682-8658-ecg-223-3-57-64
  8. Селиверстов П.В., Скворцова Т.Э., Ситкин С.И., Радченко В.Г. Неалкогольная жировая болезнь печени и желчекаменная болезнь: новый взгляд на старые взаимоотношения. Фарматека. 2018;S3:68–75. [Seliverstov P.V., Skvortsova Т.Е., Sitkin S.I., Radchenko V.G. Non-alcoholic fatty liver disease and cholelithiasis: a new view on old relationships. Farmateka. 2018;S3:68–75. (In Russ.)]. https://doi.org/10.18565/pharmateca.2018.s3.68-74
  9. Мехтиев С.Н. Билиарный сладж: нерешенные вопросы. Лечащий врач. 2007;6:24–8. [Mekhtiev S.N. Biliary sludge: unresolved issues. Lechashchiy vrach. 2007;6:24–8. (In Russ.)].
  10. Казюлин А.Н., Гончаренко А.Ю., Калягин И.Е. Применение урсодезоксихолевой кислоты в профилактике и лечении желчнокаменной болезни в практике врачей «первого контакта». Русский медицинский журнал. Медицинское обозрение. 2017;2:80–7. Kazyulin A.N., Goncharenko A.Yu., Kalyagin I.E. Application of ursodezoxycolic acid for prevention and treatment of cholelithiasis in the practice of the first contact physicians. Russian Medical Journal. MEDICAL REVIEW. 2017;2:80–7. (In Russ.)].
  11. Селезнева Э.Я., Мечетина Т.А., Орлова Ю.Н. и др. Cравнительное исследование эффективности монотерапии УДХК и комбинации УДХК с гимекромоном у больных с билиарным сладжем 2 стадии. Экспериментальная и клиническая гастроэнтерология. 2016;10(134):94–8. [Selezneva E.Ya., Mechetina T.A., Orlova Yu.N. et al. Comparative research of efficacy of monotherapy with UDCA and the combination of UDCA with gimekromon in patients with biliary sludge 2 stages. Eksperimental’naya i klinicheskaya gastroenterologiya=Experimental and Clinical Gastroenterology. 2016;134(10):94–98. (In Russ.)].
  12. Маевская М.В. Урсодезоксихолевая кислота: уникальные свойства и клиническое применение. Медицинский совет. 2023;17(8):96–105. [Maevskaya M.V. Ursodeoxycholic acid: unique properties and clinical application. Meditsinskiy sovet=Medical Council. 2023;17(8):96–105. (In Russ.)]. https://doi.org/10.21518/ms2023-136.
  13. Казюлин А.Н., Шестаков В.А., Гончаренко А.Ю. и др. Практика и перспективы клинического применения препаратов урсодезоксихолевой кислоты. Русский медицинский журнал. Медицинское обозрение. 2018;3:45–52. [Kazyulin A.N., Shestakov V.A., Goncharenko A.Yu. et al. Practice and prospects of clinical use of ursodeoxycholic acid preparations. Russian Medical Journal. Medical Review. 2018;3:45–52. (In Russ.)].
  14. Chen H., Lin L., Zou L., et al. NXT629 Ameliorates Cholesterol Gallstones in Mice Model by Improving Lipid Metabolism Disorder and Cholesterol Homeostasis Through Inhibiting the GPAM Pathway. Dig Dis Sci. 2025;70(2):612–21. https://doi.org/10.1007/s10620-024-08798-8
  15. Baik M., Kim J., Piao M.Y., et al. Deletion of liver-specific STAT5 gene alters the expression of bile acid metabolism genes and reduces liver damage in lithogenic diet-fed mice. J Nutr Biochem. 2017;39:59–67. https://doi.org/10.1016/j.jnutbio.2016.09.012
  16. Ye H.L., Zhang J.W., Chen X.Z., et al. Ursodeoxycholic acid alleviates experimental liver fibrosis involving inhibition of autophagy. Life Sci. 2020;242:117175. https://doi.org/10.1016/j.lfs.2019.117175
  17. Оковитый С.В., Райхельсон К.Л., Волнухин А.В., Кудлай Д.А. Гепатопротекторные свойства глицирризиновой кислоты. Экспериментальная и клиническая гастроэнтерология. 2020;184(12):96–108. [Okovity S.V., Raikhelson K.L., Volnukhin A.V., Kudlai D.A. Hepatoprotective properties of glycyrrhizic acid. Eksperimental’naya i klinicheskaya gastroenterologiya=Experimental and Clinical Gastroenterology. 2020;184(12):96–108. (In Russ.)]. https://doi.org/10.31146/1682-8658-ecg-184-12-96-10
  18. Yan T., Wang H., Cao L., et al. Glycyrrhizin Alleviates Nonalcoholic Steatohepatitis via Modulating Bile Acids and Meta-Inflammation. Drug Metab Dispos. 2018;46(9):1310–9. https://doi.org/10.1124/dmd.118.082008
  19. Открытое рандомизированное клиническое исследование по изучению безопасности, переносимости и фармакокинетики комбинированного лекарственного препарата Фосфоглив® УРСО (I фаза) у здоровых добровольцев. Отчет о результатах клинического исследования по протоколу 200815-FGU. Версия отчета 1.0 от 31.01.2019. [Open, randomized clinical trial to study the safety, tolerability and pharmacokinetics of the combined drug Phosphogliv® URSO (Phase I) in healthy volunteers. Report on the results of a clinical trial under protocol 200815-FGU. Report version 1.0 dated 31.01.2019. (In Russ.)].
  20. Проспективное многоцентровое открытое рандомизированное, сравнительное в параллельных группах клиническое исследование (III фаза) по протоколу 200815-FGU. Версия отчета 1.0 от 31.01.2019. [Prospective multicenter, open, randomized, comparative parallel-group clinical trial (Phase III) under protocol 200815-FGU. Report version 1.0 dated 31.01.2019. (In Russ.)].
  21. Мехтиев С.Н., Мехтиева О.А., Ибрагимова З.М. Функциональные расстройства желчного пузыря и неалкогольная жировая болезнь печени: клинические особенности и новые подходы к терапии. Медицинский совет. 2020;(15):54–64. [Mekhtiev S.N., Mekhtieva O.A., Ibragimova Z.M. Functional disorders of the gallbladder and non-alcoholic fatty liver disease: clinical features and new approaches to therapy. Meditsinskiy sovet=Medical Council. 2020;(15):54–64. (In Russ.)]. https://doi.org/10.21518/2079-701X-2020-15-54-64
  22. Мехтиев С.Н., Мехтиева О.А., Ибрагимова З.М. и др. Возможности комбинированной терапии у пациентов с функциональным билиарным расстройством сфинктера Одди. Медицинский совет. 2021;(5):102–10. [Mekhtiev S.N., Mekhtieva O.A., Ibragimova Z.M. et al. Possibilities of combination therapy in patients with functional biliary disorder of the sphincter of Oddi. Meditsinskiy sovet=Medical Council. 2021;(5):102–10. (In Russ.)]. https://doi.org/10.21518/2079-701X-2021-5-102-110
  23. Селиверстов П.В., Радченко В.Г., Дуданова О.П. и др. Результаты перорального литолиза холестеринового холецистолитиаза урсодезоксихолевой кислотой. Терапевтический архив. 2024;96(12):1206–10. [Seliverstov P.V., Radchenko V.G., Dudanova O.P., et al. Results of oral litholysis of cholesterol cholecystolithiasis with ursodeoxycholic acid. Therapeutic archive. 2024;96(12):1206–10. (In Russ.)]. https://doi.org/10.26442/00403660.2024.12.203076
  24. Яковлев А.А., Волков А.С., Баштовая О.А. и др. Клиническая эффективность и безопасность курсовой литолитической терапии больных с хроническим холециститом и билиарным сладжем препаратом ливодекса. Экспериментальная и клиническая гастроэнтерология 2015;115(3):50–4. [Yakovlev A.A., Volkov A.S., Bashtovaya O.A., et al. Clinical efficacy and safety of a course of litholytic therapy for patients with chronic cholecystitis and biliary sludge using livodexa. Eksperimental’naya i klinicheskaya gastroenterologiya=Experimental and Clinical Gastroenterology 2015;115(3):50–4. (In Russ.)].
  25. Пирогова И.Ю., Уфимцева И.В., Ушакова В.Г. и др. Диагностическая и лечебная тактика ведения пациентов с желчнокаменной болезнью. Уральский медицинский журнал. 2019;171(3):30–8. [Pirogova I.Yu., Ufimtseva I.V., Ushakova V.G. et al. Diagnostic and therapeutic tactics for managing patients with cholelithiasis. Ural Medical Journal. 2019;171(3):30–8. (In Russ.)].

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2. Figure 1. Diagram of changes in the concentration of alkaline phosphatase by visits before and after therapy with Phosphogliv® URSO (Wilcoxon test, p<0.0001)

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3. Figure 2. Diagram of changes in total cholesterol concentration by visits before and after Phosphogliv® URSO therapy (Wilcoxon test, p<0.0001)

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4. Figure З. Vеnn diagram, combination of the most common side effects during therapy with Phosphogliv® URSO

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