nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1949Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESРоль микофенолатов в иммуносупрессивной терапии: вопросы эффективности и переносимости (Обзор литературы)Role of mycophenolates in immunosuppressive therapy: issues of efficacy and tolerabilityМойсюкЯ. Г.MoysyukY. .kidneytans@mail.ruГУ НИИ трансплантологии и искусственных органов, г. МоскваRussian Federation20042706202564297300Copyright © Мойсюк Я.Г., 20252025Мойсюк Я.Г.Moysyuk Y...Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/1949

Применение микофеноловой кислоты (МФК) в виде мофетила микофенолата (ММФ) позволило добиться значительных результатов в снижении уровня острых отторжений у реципиентов почки и увеличении долгосрочной выживаемости трансплантата. Однако развитие побочных эффектов, особенно со стороны ЖКТ, часто требует снижения дозы, временного прекращения терапии или полной ее отмены, что может значительно снижать эффективность терапии ММФ. Желудочно-кишечные расстройства отмечаются почти у одной трети пациентов. Появление побочных эффектов со стороны ЖКТ приводит к достоверному снижению уровня 4-летней выживаемости трансплантата, особенно при отмене ММФ (до 70,2%). Myfortic® - улучшенная лекарственная форма микофеноловой кислоты в виде натриевой соли, покрытая кишечно-растворимой оболочкой, созданная с целью снижения токсического воздействия МФК на верхние отделы ЖКТ. У de novo реципиентов почки и пациентов, находящихся на поддерживающей терапии ММФ, myfortic® продемонстрировал терапевтическую эквивалентность с ММФ, сравнимый профиль безопасности и тенденцию к лучшей переносимости со стороны ЖКТ, позволяющую сохранять необходимую дозу препарата.

Mycophenolate mofetil (MMF), a MPA prodrug, has been shown to be an effective immunosuppressant in transplant therapy. Clinical trials in renal transplant recipients have demonstrated that MMF therapy can reduce the incidence of acute rejection episodes and improve graft survival. However MMF optimal therapy may be limited by associated side effects, in particular gastrointestinal (GI) toxicity, which may occur in 1/3 of patients. Dose changes due to GI side effects may lead to sub-therapeutic dosing and impaired clinical outcomes. GI complications were found to have detrimental effects on long-term graft survival: four-year graft survival was reduced to 70,2% in those patients with GI complications who discontinued MMF therapy. A new formulation delivering MPA - enteric-coated mycophenolate sodium (myfortic®) - has been developed to improve MPA-related upper GI adverse events. Myfortic® has demonstrated a comparable efficacy and safety profile to MMF in de novo and maintenance patients as well as the trend to lower incidence of dose changes due to GI adverse events.

мофетила микофенолатнатрия микофенолатпокрытый кишечно-растворимой оболочкойmyfortic®микофеноловая кислотаиммуносупрессияэффективностьпереносимостьReferencesAabakken L. et al. Gastroduodenal lesions associated with two different piroxicam formulations. An endoscopic comparison Scan J Gastroenterol 1992; 27: 1049-1054.Aabakken L. et al. Gastroduodenal lesions associated with two different piroxicam formulations. An endoscopic comparison Scan J Gastroenterol 1992; 27: 1049-1054.Bechgaard H., Brodie R.R., Chasseaud L.F. et al. Bioavailability of indomethacin from two multiple-units controlled-release formulations. Eur J Clin Pharmacol 1982; 21: 511-515.Bechgaard H., Brodie R.R., Chasseaud L.F. et al. Bioavailability of indomethacin from two multiple-units controlled-release formulations. Eur J Clin Pharmacol 1982; 21: 511-515.Budde K., Curtis J., Knoll G. et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant 2004; 4: 237-243.Budde K., Curtis J., Knoll G. et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant 2004; 4: 237-243.Budde K., Glander P., Braun K. et al. Pharmacokinetics and pharmacodynamics of mycophenolate mofetil and enteric-coated mycophenolate in stable renal allograft recipients. Transplantation 2004; 78 (2; Suppl. 1): 459-460.Budde K., Glander P., Braun K. et al. Pharmacokinetics and pharmacodynamics of mycophenolate mofetil and enteric-coated mycophenolate in stable renal allograft recipients. Transplantation 2004; 78 (2; Suppl. 1): 459-460.Caldwell J.R., Roth S.H., the Naproxen EC Study Group. A double blind study comparing the efficacy and safety of enteric coated naproxen to naproxen in the management of NSAID intolerant patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 1994; 21: 689-695.Caldwell J.R., Roth S.H., the Naproxen EC Study Group. A double blind study comparing the efficacy and safety of enteric coated naproxen to naproxen in the management of NSAID intolerant patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 1994; 21: 689-695.Cole A.T. et al. Protection of human gastric mucosa against aspirin-enteric coating or dose reduction? Aliment Pharmacol Ther 1999; 13: 187-193.Cole A.T. et al. Protection of human gastric mucosa against aspirin-enteric coating or dose reduction? Aliment Pharmacol Ther 1999; 13: 187-193.Dammann H.G., Burkhardt F., Wolf N. Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions. Aliment Pharmacol Ther 1999; 13: 1109-1114.Dammann H.G., Burkhardt F., Wolf N. Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions. Aliment Pharmacol Ther 1999; 13: 1109-1114.ERLW152. Enteric-coated mycophenolate sodium (EC-MPS, myfortic®) delivers bioequivalent MPA exposure compared to mycophenolate mofetil. Data on file. Novartis Pharma AG/Novartis Pharmaceuticals Corporation 2004.ERLW152. Enteric-coated mycophenolate sodium (EC-MPS, myfortic®) delivers bioequivalent MPA exposure compared to mycophenolate mofetil. Data on file. Novartis Pharma AG/Novartis Pharmaceuticals Corporation 2004.European Mycophenolate Mofetil Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection. Lancet 1995; 345: 1321-1325.European Mycophenolate Mofetil Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporine and corticosteroids for prevention of acute rejection. Lancet 1995; 345: 1321-1325.Ferguson R.M., Porterfield-Baxa J., Tierce J.C. et al. The cost of mycophenolate mofetil-related (MMF) gastrointestinal adverse events and impact of MMF dose-reductions/discontinuations on acute rejection in transplanted patients. Presented at the European Society for Organ Transplantation. Venice, Italy: 20-24 September 2003; Abstract 707.Ferguson R.M., Porterfield-Baxa J., Tierce J.C. et al. The cost of mycophenolate mofetil-related (MMF) gastrointestinal adverse events and impact of MMF dose-reductions/discontinuations on acute rejection in transplanted patients. Presented at the European Society for Organ Transplantation. Venice, Italy: 20-24 September 2003; Abstract 707.Haeberlin B., Mak C.P., Meinzer A., Vonderscher J. Enteric-coated pharmaceutical compositions. US Patent 6,172,107, filed 22 December 22 1999.Haeberlin B., Mak C.P., Meinzer A., Vonderscher J. Enteric-coated pharmaceutical compositions. US Patent 6,172,107, filed 22 December 22 1999.Hardinger K.L., Brennan D.C., Lowell J. et al. Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil. Transplant Int 2004 (in press).Hardinger K.L., Brennan D.C., Lowell J. et al. Long-term outcome of gastrointestinal complications in renal transplant patients treated with mycophenolate mofetil. Transplant Int 2004 (in press).Hariharan S., Johnson C.P., Bresnahan B.A. et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342: 605-612.Hariharan S., Johnson C.P., Bresnahan B.A. et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342: 605-612.Hawthorne A.B., Mahida Y.R., Cole A.T. et al. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis. Br J Clin Pharmacol 1991; 32: 77-83.Hawthorne A.B., Mahida Y.R., Cole A.T. et al. Aspirin-induced gastric mucosal damage: prevention by enteric-coating and relation to prostaglandin synthesis. Br J Clin Pharmacol 1991; 32: 77-83.Knoll G.A., MacDonald I., Khan A. et al. Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation. J Am Soc Nephrol 2003; 14: 2381-2386.Knoll G.A., MacDonald I., Khan A. et al. Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation. J Am Soc Nephrol 2003; 14: 2381-2386.Ojo A.O., Meier-Kriesche H.-U., Hanson J.A. et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000; 69: 2405-2409.Ojo A.O., Meier-Kriesche H.-U., Hanson J.A. et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000; 69: 2405-2409.Pelletier R.P., Akin B., Henry M.L. et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clin Transplant 2003; 17: 200-205.Pelletier R.P., Akin B., Henry M.L. et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clin Transplant 2003; 17: 200-205.Salvadori M., Holzer H., De Mattos A. et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 2004; 4: 231-236.Salvadori M., Holzer H., De Mattos A. et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 2004; 4: 231-236.Schmouder R., Arns W., Merkel F. et al. Pharmacokinetics of ERL080A: a new enteric coated formulation of mycophenolic acid-sodium. Transplantation 1993; 67 (7): S203.Schmouder R., Arns W., Merkel F. et al. Pharmacokinetics of ERL080A: a new enteric coated formulation of mycophenolic acid-sodium. Transplantation 1993; 67 (7): S203.Sollinger H.W. for the US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60: 225-232.Sollinger H.W. for the US Renal Transplant Mycophenolate Mofetil Study Group. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995; 60: 225-232.Takemoto S.K. Maintenance immunosuppression. Cecka J.M. and Terasaki P.I. (eds). In: 16th Annual Volume Clinical Transplantations, UCLA Immunogenetics Center, USA: 2000: 481-495. Available at http://wwwpathnet.medsch.ucla.edu/education/index.htmTakemoto S.K. Maintenance immunosuppression. Cecka J.M. and Terasaki P.I. (eds). In: 16th Annual Volume Clinical Transplantations, UCLA Immunogenetics Center, USA: 2000: 481-495. Available at http://wwwpathnet.medsch.ucla.edu/education/index.htmThe Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection on cadaveric renal transplantation. Transplantation 1996; 61: 1029-1037.The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection on cadaveric renal transplantation. Transplantation 1996; 61: 1029-1037.

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