medbioМедико-биологические проблемы жизнедеятельностиMedical and Biological Problems of Life Activity2074-2088Республиканский научно-практический центр радиационной медицины и экологии человека10.58708/2074-2088.2024-2(32)-100-104medbio-401Research ArticleКЛИНИЧЕСКАЯ МЕДИЦИНАCLINICAL MEDICINEДинамика уровня такролимуса у реципиентов почечного трансплантатаDynamics of tacrolimus levels in renal transplant recipientshttps://orcid.org/0000-0002-0968-6630ЗыблевС. Л.ZyblevS. L.

г. Гомель

s.zyblev@yandex.ruСилинА. Е.SilinA. E.

г. Гомель

МартинковВ. Н.MartinkovV. N.

г. Гомель

ЗыблеваС. В.ZyblevaS. V.

г. Гомель

ВеличкоА. В.VelichkoA. V.

г. Гомель

КабешевБ. О.KabeshevB. O.

г. Гомель

ГУ «РНПЦ радиационной медицины и экологии человека»Belarus20240110202402100104Copyright © Зыблев С.Л., Силин А.Е., Мартинков В.Н., Зыблева С.В., Величко А.В., Кабешев Б.О., 20242024Зыблев С.Л., Силин А.Е., Мартинков В.Н., Зыблева С.В., Величко А.В., Кабешев Б.О.Zyblev S.L., Silin A.E., Martinkov V.N., Zybleva S.V., Velichko A.V., Kabeshev B.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medbio.ejournal.by/jour/article/view/401

Оценен уровень такролимуса у реципиентов почечного трансплантата на 3-и, 10-е и 30-е сутки после трансплантации почки. Все пациенты получали трехкомпонентную иммуносупрессивную терапию: ингибитор кальциневрина (такролимус), антипролиферативные лекарственные средства (азатиоприн или мофетил микофенолата) и преднизолон. Такролимус применялся в дозе 0,1 мг/кг в сутки. По нашим данным, концентрация такролимуса на 3-и сутки равнялась 5,2 [4,1; 5,5] нг/мл, на 10-е сутки составила 5,1 [2,5; 7,4] нг/мл (р3,10 =0,809), на 30-е сутки после операции уровень такролимуса достиг показателя 8,2 [4,6; 10,2] нг/мл (р10,30 =0,0007 и р3,30 =0,027). Таким образом, при назначении такролимуса в рекомендованных дозировках у 8,6% реципиентов почечного трансплантата через месяц после операции концентрация препарата не превышала 4 нг/мл. При этом у 71% реципиентов почечного трансплантата на 30-е сутки послеоперационного периода концентрация такролимуса была выше 7 нг/мл.

We studied 35 medical histories of renal transplant recipients who underwent kidney transplantation in the surgical department (transplantation, reconstructive and endocrine surgery) of RRCRM&HE in Gomel. Tacrolimus concentrations were assessed on days 3, 10, and 30 after kidney transplantation. The tacrolimus C0 (zero concentration) level was determined fasting, before the morning administration of medications. Among kidney transplant recipients, there were 19 (54,3%) men and 16 (45,7%) women. The mean age was 42,7±2,0 years [95% CI 38,58; 46,73]. Before transplantation, 91,4% of patients were on programmed hemodialysis and 8.6% on peritoneal dialysis. All patients received triple immunosuppressive therapy: a calcineurin inhibitor (tacrolimus), antiproliferative drugs (azathioprine or mycophenolate mofetil), and prednisolone. Tacrolimus was administered at a dose of 0,1 mg/kg per day. According to our data, the concentration of tacrolimus on day 3 was 5,2 [4,1; 5,5] ng/ml, on day 10 it was 5,1 [2,5; 7,4] ng/ml (p3,10 = 0,809), on day 30 after surgery the tacrolimus level reached 8,2 [4,6; 10,2] ng/ml (p10,30 = 0,0007 and p3,30 = 0,027). Thus, when tacrolimus was administered at recommended doses, 8,6% of renal transplant recipients failed to achieve concentrations exceeding 4 ng/ml one month after surgery. Moreover, on day 30 of the postoperative period, the concentration of tacrolimus exceeded 7 ng/ml in 71% of renal transplant recipients.

иммуносупрессивная терапияконцентрация такролимусатрансплантация почкиCYP3A4фармакогеномикаtacrolimus concentrationkidney transplantationReferencesRabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial / O. Thomusch [et al.] // Lancet. – 2017. – № 388. – Р. 3006-3016.Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal transplantation (Harmony): an open-label, multicentre, randomised controlled trial / O. Thomusch [et al.] // Lancet. – 2017. – № 388. – Р. 3006-3016.Use of pharmacogenetics to optimize immunosuppressant therapy in kidney-transplanted patients / V. Urzì Brancati [et al.] // Biomedicines. – 2022. – Vol. 10, №8. – Р. 1798.Use of pharmacogenetics to optimize immunosuppressant therapy in kidney-transplanted patients / V. Urzì Brancati [et al.] // Biomedicines. – 2022. – Vol. 10, №8. – Р. 1798.Correlation between gene polymorphism and blood concentration of calcineurin inhibitors in renal transplant recipients: An overview of systematic reviews / L. Su [et al.] // Medicine (Baltimore). – 2019. – № 26. – Р. 16113.Correlation between gene polymorphism and blood concentration of calcineurin inhibitors in renal transplant recipients: An overview of systematic reviews / L. Su [et al.] // Medicine (Baltimore). – 2019. – № 26. – Р. 16113.Wolf, U. A drug safety concept (I) to avoid polypharmacy risks in transplantation by individual pharmacotherapy management in therapeutic drug monitoring of immunosuppressants / U. Wolf // Pharmaceutics. – 2023. – Vol. 15, №9. – Р. 2300.Wolf, U. A drug safety concept (I) to avoid polypharmacy risks in transplantation by individual pharmacotherapy management in therapeutic drug monitoring of immunosuppressants / U. Wolf // Pharmaceutics. – 2023. – Vol. 15, №9. – Р. 2300.Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence / N. Issa [et al.] // Am J Nephrol. – 2013. – Vol. 37, №6. – Р. 602-612.Calcineurin inhibitor nephrotoxicity: a review and perspective of the evidence / N. Issa [et al.] // Am J Nephrol. – 2013. – Vol. 37, №6. – Р. 602-612.Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients / L.M. Andrews [et al.] // Expert Opin Drug Metab Toxicol. – 2017. – Vol. 13, №12. – Р. 1225-1236.Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients / L.M. Andrews [et al.] // Expert Opin Drug Metab Toxicol. – 2017. – Vol. 13, №12. – Р. 1225-1236.The challenge of achieving target drug concentrations in clinical trials: experience from the Symphony study / H. Ekberg [et al.] // Transplantation. – 2009. – № 87. – Р. 1360-1366.The challenge of achieving target drug concentrations in clinical trials: experience from the Symphony study / H. Ekberg [et al.] // Transplantation. – 2009. – № 87. – Р. 1360-1366.Reduction of extended-release tacrolimus dose in low-immunological-risk kidney transplant recipients increases risk of rejection and appearance of donor-specific antibodies: a randomized study / P. Gatault [et al.] // Am J Transplant. – 2017. – № 17. – Р. 1370-1379.Reduction of extended-release tacrolimus dose in low-immunological-risk kidney transplant recipients increases risk of rejection and appearance of donor-specific antibodies: a randomized study / P. Gatault [et al.] // Am J Transplant. – 2017. – № 17. – Р. 1370-1379.Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the european consensus conference / P. Wallemacq [et al.] // Ther Drug Monit. – 2009. – Vol. 31, №2. – Р. 139-152.Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the european consensus conference / P. Wallemacq [et al.] // Ther Drug Monit. – 2009. – Vol. 31, №2. – Р. 139-152.Therapeutic drug monitoring of Tacrolimus-Personalized therapy: second Consensus Report / M. Brunet [et al.] // Ther Drug Monit. – 2019. – Vol. 41, №3. – Р. 261-307.Therapeutic drug monitoring of Tacrolimus-Personalized therapy: second Consensus Report / M. Brunet [et al.] // Ther Drug Monit. – 2019. – Vol. 41, №3. – Р. 261-307.Vanhove, T. Clinical determinants of calcineurin inhibitor disposition: a mechanistic review / T. Vanhove, P. Annaert, D.R.J. Kuypers // Drug Metab Rev. – 2016. – Vol. 48, №1. – Р. 88-112.Vanhove, T. Clinical determinants of calcineurin inhibitor disposition: a mechanistic review / T. Vanhove, P. Annaert, D.R.J. Kuypers // Drug Metab Rev. – 2016. – Vol. 48, №1. – Р. 88-112.Pharmacogenomics of old and new immunosuppressive drugs for precision medicine in kidney transplantation / S. Turolo [et al.] // Journal of clinical medicine. – 2023. – Vol. 12, №13. – Р. 4454.Pharmacogenomics of old and new immunosuppressive drugs for precision medicine in kidney transplantation / S. Turolo [et al.] // Journal of clinical medicine. – 2023. – Vol. 12, №13. – Р. 4454.Wysocki, K. Pharmacogenomics in clinical care / K. Wysocki, D. Seibert // J. Am. Assoc. Nurse Pract. – 2019. – Vol. 31. – Р. 443-446.Wysocki, K. Pharmacogenomics in clinical care / K. Wysocki, D. Seibert // J. Am. Assoc. Nurse Pract. – 2019. – Vol. 31. – Р. 443-446.Non-linear relationship between tacrolimus blood concentration and acute rejection after kidney transplantation: a systematic review and dose-response meta-analysis of cohort studies / S. Yin [et al.] // Curr. Pharm. Des. – 2019. – Vol. 25. – Р. 2394-2403.Non-linear relationship between tacrolimus blood concentration and acute rejection after kidney transplantation: a systematic review and dose-response meta-analysis of cohort studies / S. Yin [et al.] // Curr. Pharm. Des. – 2019. – Vol. 25. – Р. 2394-2403.

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