Population Pharmacokinetic Modelling of Unbound Mycophenolic Acid and its Glucuronide in Adult Kidney Transplant Recipients in Early Post-Transplant

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Kiang TK, Ensom MH. Anti-rejection drugs. In: Murphy JE, editor. Clinical pharmacokinetics. 6th ed. Bethesda: American Society of Health-System Pharmacists; 2017. p. 205–20.

Google Scholar 

Kiang TK, Ensom MH. Immunosuppressants. In: Beringer, editor. Basic clinical pharmacokinetics. Philadelphia: Wolters Kluwer; 2017. p. 320–58.

Google Scholar 

Bergan S, Brunet M, Hesselink DA, Johnson-Davis KL, Kunicki PK, Lemaitre F, et al. Personalized therapy for mycophenolate: consensus report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit. 2021;43(2):150–200. https://doi.org/10.1097/FTD.0000000000000871.

Article  PubMed  CAS  Google Scholar 

Rong Y, Patel V, Kiang TKL. Recent lessons learned from population pharmacokinetic studies of mycophenolic acid: physiological, genomic, and drug interactions leading to the prediction of drug effects. Expert Opin Drug Metab Toxicol. 2022;17(12):1369–406. https://doi.org/10.1080/17425255.2021.2027906.

Article  Google Scholar 

Staatz CE, Tett SE. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients. Clin Pharmacokinet. 2007;46(1):13–58. https://doi.org/10.2165/00003088-200746010-00002.

Article  PubMed  CAS  Google Scholar 

Staatz CE, Tett SE. Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update. Arch Toxicol. 2014;88(7):1351–89. https://doi.org/10.1007/s00204-014-1247-1.

Article  PubMed  CAS  Google Scholar 

de Winter BC, van Gelder T, Sombogaard F, Shaw LM, van Hest RM, Mathot RA. Pharmacokinetic role of protein binding of mycophenolic acid and its glucuronide metabolite in renal transplant recipients. J Pharmacokinet Pharmacodyn. 2009;36(6):541–64. https://doi.org/10.1007/s10928-009-9136-6.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Benjanuwattra J, Pruksakorn D, Koonrungsesomboon N. Mycophenolic acid and its pharmacokinetic drug-drug interactions in humans: review of the evidence and clinical implications. J Clin Pharmacol. 2020;60(3):295–311. https://doi.org/10.1002/jcph.1565.

Article  PubMed  CAS  Google Scholar 

Sherwin CM, Fukuda T, Brunner HI, Goebel J, Vinks AA. The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011;50(1):1–24. https://doi.org/10.2165/11536640-000000000-00000.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kiang TKL, Ensom MHH. Population pharmacokinetics of mycophenolic acid: an update. Clin Pharmacokinet. 2018;57(5):547–58. https://doi.org/10.1007/s40262-017-0593-6.

Article  PubMed  CAS  Google Scholar 

Kiang TKL, Ensom MHH. Exposure-toxicity relationships of mycophenolic acid in adult kidney transplant patients. Clin Pharmacokinet. 2019;58(12):1533–52. https://doi.org/10.1007/s40262-019-00802-z.

Article  CAS  Google Scholar 

Atcheson BA, Taylor PJ, Mudge DW, Johnson DW, Hawley CM, Campbell SB, et al. Mycophenolic acid pharmacokinetics and related outcomes early after renal transplant. Br J Clin Pharmacol. 2005;59(3):271–80. https://doi.org/10.1111/j.1365-2125.2004.02235.x.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kaplan B, Gruber SA, Nallamathou R, Katz SM, Shaw LM. Decreased protein binding of mycophenolic acid associated with leukopenia in a pancreas transplant recipient with renal failure. Transplantation. 1998;65(8):1127–9. https://doi.org/10.1097/00007890-199804270-00019.

Article  PubMed  CAS  Google Scholar 

Weber LT, Shipkova M, Armstrong VW, Wagner N, Schutz E, Mehls O, et al. The pharmacokinetic-pharmacodynamic relationship for total and free mycophenolic acid in pediatric renal transplant recipients: a report of the German study group on mycophenolate mofetil therapy. J Am Soc Nephrol. 2002;13(3):759–68. https://doi.org/10.1681/ASN.V133759.

Article  Google Scholar 

Jacobson P, Rogosheske J, Barker JN, Green K, Ng J, Weisdorf D, et al. Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther. 2005;78(5):486–500. https://doi.org/10.1016/j.clpt.2005.08.009.

Article  PubMed  CAS  Google Scholar 

Frymoyer A, Verotta D, Jacobson P, Long-Boyle J. Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors. Br J Clin Pharmacol. 2013;75(2):463–75. https://doi.org/10.1111/j.1365-2125.2012.04372.x.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kiang TK, Ensom MH. Therapeutic drug monitoring of mycophenolate in adult solid organ transplant patients: an update. Expert Opin Drug Metab Toxicol. 2016;12(5):545–53. https://doi.org/10.1517/17425255.2016.1170806.

Article  PubMed  CAS  Google Scholar 

Metz DK, Holford N, Kausman JY, Walker A, Cranswick N, Staatz CE, et al. Optimizing mycophenolic acid exposure in kidney transplant recipients: time for target concentration intervention. Transplantation. 2019;103(10):2012–30. https://doi.org/10.1097/TP.0000000000002762.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Villeneuve C, Humeau A, Monchaud C, Labriffe M, Rerolle JP, Couzi L, et al. Better rejection-free survival at three years in kidney transplant recipients with model-informed precision dosing of mycophenolate mofetil. Clin Pharmacol Ther. 2024;116(2):351–62. https://doi.org/10.1002/cpt.3206.

Article  PubMed  CAS  Google Scholar 

Lentine KL, Smith JM, Lyden GR, Miller JM, Dolan TG, Bradbrook K, et al. OPTN/SRTR 2022 annual data report: kidney. Am J Transplant. 2024;24(2S1):S19–118. https://doi.org/10.1016/j.ajt.2024.01.012.

Article  PubMed  Google Scholar 

Raval AD, Kistler KD, Tang Y, Vincenti F. Burden of neutropenia and leukopenia among adult kidney transplant recipients: a systematic literature review of observational studies. Transpl Infect Dis. 2023;25(1):e14000. https://doi.org/10.1111/tid.14000.

Article  PubMed  Google Scholar 

van Gelder T, Hilbrands LB, Vanrenterghem Y, Weimar W, de Fijter JW, Squifflet JP, et al. A randomized double-blind, multicenter plasma concentration controlled study of the safety and efficacy of oral mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. Transplantation. 1999;68(2):261–6. https://doi.org/10.1097/00007890-199907270-00018.

Article  PubMed  Google Scholar 

van Gelder T. How cyclosporine reduces mycophenolic acid exposure by 40% while other calcineurin inhibitors do not. Kidney Int. 2021;100(6):1185–9. https://doi.org/10.1016/j.kint.2021.06.036.

Article  PubMed  CAS  Google Scholar 

van Hest RM, van Gelder T, Bouw R, Goggin T, Gordon R, Mamelok RD, et al. Time-dependent clearance of mycophenolic acid in renal transplant recipients. Br J Clin Pharmacol. 2007;63(6):741–52. https://doi.org/10.1111/j.1365-2125.2006.02841.x.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rong Y, Mayo P, Ensom MHH, Kiang TKL. Population pharmacokinetics of mycophenolic acid co-administered with tacrolimus in corticosteroid-free adult kidney transplant patients. Clin Pharmacokinet. 2019;58(11):1483–95. https://doi.org/10.1007/s40262-019-00771-3.

Article  PubMed  CAS  Google Scholar 

Zafrani L, Truffaut L, Kreis H, Etienne D, Rafat C, Lechaton S, et al. Incidence, risk factors and clinical consequences of neutropenia following kidney transplantation: a retrospective study. Am J Transplant. 2009;9(8):1816–25. https://doi.org/10.1111/j.1600-6143.2009.02699.x.

Article  PubMed  CAS  Google Scholar 

McAdams-DeMarco MA, Law A, Tan J, Delp C, King EA, Orandi B, et al. Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients. Transplantation. 2015;99(4):805–10. https://doi.org/10.1097/TP.0000000000000444.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ji SM, Xie KN, Chen JS, Wen JQ, Cheng DR, Li X, et al. Retrospective evaluation of the effect of mycophenolate mofetil dosage on survival of kidney grafts based on biopsy results. Transplant Proc. 2014;46(10):3383–9. https://doi.org/10.1016/j.transproceed.2014.09.107.

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