327
Views
33
CrossRef citations to date
0
Altmetric
Review

Mycophenolic acid trough level monitoring in solid organ transplant recipients treated with mycophenolate mofetil: association with clinical outcome

Pages 2355-2364 | Accepted 22 Sep 2006, Published online: 23 Oct 2006

References

  • Meier-Kriesche HU, Steffen BJ, Hochberg AM, et al. Mycophenolate mofetil versus azathioprine therapy is associated with a significant protection against long-term renal allograft function deterioration. Transplantation 2003;75:1341–6
  • Srinivas TR, Kaplan B, Schold JD, Meier-Kriesche HU. The impact of mycophenolate mofetil on long-term outcomes in kidney transplantation. Transplantation 2005;80(Suppl 2):S211–S220
  • Hosenpud JD, Bennett LE. Mycophenolate mofetil versus azathioprine in patients surviving the initial cardiac transplant hospitalization: an analysis of the Joint UNOS/ISHLT Thoracic Registry. Transplantation 2001;72:1662–5
  • Lake JR, Shorr JS, Steffen BJ, et al. Differential effects of donor age in liver transplant recipients infected with hepatitis B, hepatitis C and without viral hepatitis. Am J Transplant 2005;5:549–57
  • Ojo AO, Meier-Kriesche HU, Hanson JA, et al. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation 2000;69:2405–9
  • David KM, Morris JA, Steffen BJ, et al. Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre-transplant diabetes. Clin Transplant 2005;19:279–85
  • Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000;69:1252–60
  • Flechner SM, Feng J, Mastroianni B, et al. The effect of 2-gram versus 1-gram concentration controlled mycophenolate mofetil on renal transplant outcomes using sirolimus-based calcineurin inhibitor drug-free immunosuppression. Transplantation 2005;79:926–34
  • Takemoto SK. Patterns and outcomes for maintenance immunosuppression in the UNOS Renal Transplant Registry. Am J Transplant 2002;2(Suppl):A42
  • Meier-Kriesche HU, Li S, Gruessner RW, et al. Immuno-suppression: evolution in practice and trends, 1994–2004. Am J Transplant 2006;6(5 Pt 2):1111–31
  • Van Gelder T. Mycophenolate mofetil: how to further improve using an already successful drug? Am J Transplant 2005;5: 199–200
  • Shaw LM, Holt DW, Oellerich M, et al. Current issues in therapeutic drug monitoring of mycophenolic acid: report of a roundtable discussion. Ther Drug Monit 2001;23:305–15
  • Van Gelder T, Meur YL, Shaw LM, et al. Therapeutic drug monitoring of mycophenolate mofetil in transplantation. Ther Drug Monit 2006;28:145–54
  • Halloran PF. Immunosuppressive drugs for kidney transplantation. New Engl J Med 2004;351:2715–29
  • Morris RG. Immunosuppressant drug monitoring: is the laboratory meeting clinical expectations? Ann Pharmacother 2005;39: 119–27
  • Tredger JM, Brown NW. Mycophenolate: better value through monitoring? Transplantation 2006;81:507–8
  • Hale MD, Nicholls AJ, Bullingham RE, et al. The pharmaco-kinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Pharmacol Ther 1998;64:672–83
  • Van Gelder T, Hilbrands LB, Vanrenterghem Y, 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;68:261–6
  • Barbari A, Stephan A, Masri MA, et al. Mycophenolic acid plasma trough level: correlation with clinical outcome. Exp Clin Transplant 2005;3:355–60
  • Borrows R, Chusney G, Loucaidou M, et al. Mycophenolic acid 12-h trough level monitoring in renal transplantation: association with acute rejection and toxicity. Am J Transplant 2006;6:121–8
  • Budde K, Tedesco H, Pestana JM, et al. Mean mycophenolic acid trough level (MPA C0) is 25% higher for myfortic compared to MMF due to delayed release formulation. Transplantion 2006; 82(1 Suppl 2):999
  • Bullingham RES, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet 1998;34:429–55
  • Kelly P, Kahan BD. Review: metabolism of immunosuppressant drugs. Curr Drug Metab 2002;3:275–87
  • Shaw LM, Korecka M, Venkataramanan R, et al. Mycophenolic acid pharmacodynamics and pharmacokinetics provide a basis for rational monitoring strategies. Am J Transplant 2003;3:534–42
  • Shipkova M, Strassburg CP, Braun F, et al. Glucuronide and glucoside conjugation of mycophenolic acid by human liver, kidney and intestinal microsomes. Br J Pharmacol 2001;132:1027–34
  • Van Hest RM, Hesselink DA, Vulto AG, et al. Individualisation of mycophenolate mofetil dose in renal transplant recipients. Expert Opin Pharmacother 2006;7:361–76
  • Van Hest RM, van Gelder T, Vulto AG, Mathot RA. Population pharmacokinetics of mycophenolic acid in renal transplant recipients. Clin Pharmacokinet 2005;44:1083–96
  • Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil. Clin Transplant 1996;10:77–84
  • Sintchak MD, Fleming MA, Futer O, et al. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell 1996;85:921–30
  • Ransom JT. Mechanism of action of mycophenolate mofetil. Ther Drug Monit 1995;17:681–4
  • Langman LJ, LeGatt DF, Halloran PF, Yatscoff RW. Pharmaco-dynamic assessment of mycophenolic acid-induced immuno-suppression in renal transplant recipients. Transplantation 1996;62:666–72
  • Millan O, Oppenheimer F, Brunet M, et al. Assessment of mycophenolic acid-induced immunosuppression: a new approach. Clin Chem 2000;46:1376–83
  • Budde K, Braun KP, Glander P, et al. Pharmacodynamic monitoring of mycophenolate mofetil in stable renal allograft recipients. Transplant Proc 2002;34:1748–50
  • Budde K, Glander P, Bauer S, et al. Pharmacodynamic monitoring of mycophenolate mofetil. Clin Chem Lab Med 2000;38:1213–6
  • Kuypers DR. Immunosuppressive drug monitoring – what to use in clinical practice today to improve renal graft outcome. Transplant Int 2005;18:140–50
  • Schütz E, Armstrong VW, Shipkova M, et al. Limited sampling strategy for the determination of mycophenolic acid area under the curve in pediatric kidney recipients [German Study Group on MMF Therapy in Pediatric Renal Transplant Recipients]. Transplant Proc 1998;30:1182–4
  • Johnson AG, Rigby RJ, Taylor PJ, et al. The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients. Clin Pharmacol Ther 1999;66:492–500
  • Filler G, Mai I. Limited sampling strategy for mycophenolic acid area under the curve. Ther Drug Monit 2000;22:169–73
  • Pawinski T, Hale M, Korecka M, et al. Limited sampling strategy for the estimation of mycophenolic acid area under the curve in adult renal transplant patients treated with concomitant tacrolimus. Clin Chem 2002;48:1497–504
  • Cox VC, Ensom MH. Mycophenolate mofetil for solid organ transplantation: does the evidence support the need for clinical pharmacokinetic monitoring? Ther Drug Monit 2003;25:137–57
  • Shaw LM, Nawrocki A, Korecka M, et al. Using established immunosuppressant therapy effectively: lessons from the measurement of mycophenolic acid plasma concentrations. Ther Drug Monit 2004;26:347–51
  • Mardigyan V, Tchervenkov J, Metrakos P, et al. Best single time points as surrogates to the tacrolimus and mycophenolic acid area under the curve in adult liver transplant patients beyond 12 months of transplantation. Clin Ther 2005;27:463–9
  • Mardigyan V, Giannetti N, Cecere R, et al. Best single time points to predict the area-under-the-curve in long-term heart transplant patients taking mycophenolate mofetil in combination with cyclosporine or tacrolimus. J Heart Lung Transplant 2005;24:1614–8
  • Baraldo M, Isola M, Feruglio MT, et al. Therapeutic mycophenolic acid monitoring by means of limited sampling strategy in orthotopic heart transplant patients. Transplant Proc 2005;37:2240–3
  • Van Hest RM, Mathot RA, Vulto AG, et al. Within-patient variability of mycophenolic acid exposure: therapeutic drug monitoring from a clinical point of view. Ther Drug Monit 2006;28:31–4
  • Nowak I, Shaw LM. Mycophenolic acid binding to human serum albumin: characterization and relation to pharmacodynamics. Clin Chem 1995;41:1011–7
  • Shaw LM, Korecka M, Aradhye S, et al. Mycophenolic acid area under the curve values in African American and Caucasian renal transplant patients are comparable. J Clin Pharmacol 2000;40:624–33
  • Kaplan B, Meier-Kriesche HU, Friedman G, et al. The effect of renal insufficiency on mycophenolic acid protein binding. J Clin Pharmacol 1999;39:715–20
  • Weber LT, Shipkova M, Lamersdorf T, et al. Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients [German Study group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients]. J Am Soc Nephrol 1998;9:1511–20
  • Van Hest RM, Mathot RA, Pescovitz MD, et al. Explaining variability in mycophenolic acid exposure to optimize mycophenolate mofetil dosing: a population pharmacokinetic meta-analysis of mycophenolic acid in renal transplant recipients. J Am Soc Nephrol 2006;17:871–80
  • Hesselink DA, van Gelder T. Genetic and nongenetic determinants of between-patient variability in the pharmacokinetics of mycophenolic acid. Clin Pharmacol Ther 2005;78:317–21
  • Buchler M, Lebranchu Y, Beneton M, et al. Higher exposure to mycophenolic acid with sirolimus than with cyclosporine cotreatment. Clin Pharmacol Ther 2005;78:34–42
  • Smak Gregoor PJ, de Sevaux RG, Hene RJ, et al. Effect of cyclosporine on mycophenolic acid trough levels in kidney transplant recipients. Transplantation 1999;68:1603–6
  • Cremers S, Schoemaker R, Scholten E, et al. Characterizing the role of enterohepatic recycling in the interactions between mycophenolate mofetil and calcineurin inhibitors in renal transplant patients by pharmacokinetic modelling. Br J Clin Pharmacol 2005;60:249–56
  • Hesselink DA, van Hest RM, Mathot RA, et al. Cyclosporine interacts with mycophenolic acid by inhibiting the multidrug resistance-associated protein 2. Am J Transplant 2005; 5:987–94
  • Westley IS, Brogan LR, Morris RG, et al. Role of Mrp2 in the hepatic disposition of mycophenolic acid and its glucuronide metabolites: effect of cyclosporine. Drug Metab Dispos 2006;34:261–6
  • Kiberd BA, Lawen J, Fraser AD, et al. Early adequate mycophenolic acid exposure is associated with less rejection in kidney transplantation. Am J Transplant 2004;4:1079–83
  • Kuypers DR, Claes K, Evenepoel P, et al. Long-term changes in mycophenolic acid exposure in combination with tacrolimus and corticosteroids are dose dependent and not reflected by trough plasma concentration: a prospective study in 100 de novo renal allograft recipients. J Clin Pharmacol 2003;43:866–80
  • Kuypers DR, Claes K, Evenepoel P, et al. Clinical efficacy and toxicity profile of tacrolimus and mycophenolic acid in relation to combined long-term pharmacokinetics in de novo renal allograft recipients. Clin Pharmacol Ther 2004;75:434–47
  • Bloom R, Naraghi R, Cibrik D, et al. OptiCept trial: interim results of 6-month efficacy and safety of monitored mycophenolate mofetil (MMF) in combination with CNI in renal transplantation. Transplantion 2006;82(1 Suppl 2):344
  • DeNofrio D, Loh E, Kao A, et al. Mycophenolic acid concentrations are associated with cardiac allograft rejection. J Heart Lung Transplant 2000;19:1071–6
  • Meiser BM, Groetzner J, Kaczmarek I, et al. Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients? Transplantation 2004;78:591–8
  • Petrakopoulou P, Anthopoulou L, Muscholl M, et al. Coronary endothelial vasomotor function and vascular remodeling in heart transplant recipients randomized for tacrolimus or cyclosporine immunosuppression. J Am Coll Cardiol 2006;47:1622–9
  • Tredger JM, Brown NW, Adams J, et al. Monitoring mycophenolate in liver transplant recipients: toward a therapeutic range. Liver Transplant 2004;10:492–502
  • Venkataramanan R, Shaw LM. Therapeutic monitoring of mycophenolic acid in liver transplant patients. Liver Transplant 2004;10:503–5
  • Van Gelder T, Shaw LM. The rationale for and limitations of therapeutic drug monitoring for mycophenolate mofetil in transplantation. Transplantation 2005;80(Suppl 2):S244–S253
  • Brunet M, Cirera I, Martorell J, et al. Sequential determination of pharmacokinetics and pharmacodynamics of mycophenolic acid in liver transplant patients treated with mycophenolate mofetil. Transplantation 2006;81:541–6
  • Glander P, Hambach P, Braun KP, et al. Pre-transplant inosine monophosphate dehydrogenase activity is associated with clinical outcome after renal transplantation. Am J Transplant 2004;4:2045–51
  • Wieland E, Shipkova M, Schellhaas U, et al. Induction of cytokine release by the acyl glucuronide of mycophenolic acid: a link to side effects? Clin Biochem 2000;33:107–13
  • Kaplan B, Gruber SA, Nallamathou R, et al. Decreased protein binding of mycophenolic acid associated with leucopenia in a pancreas transplant recipient with renal failure. Transplantation 1998;65:1127–9
  • Weber LT, Shipkova M, Armstrong VW, 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;13:759–68
  • Mudge DW, Atcheson BA, Taylor PJ, et al. Severe toxicity associated with a markedly elevated mycophenolic acid free fraction in a renal transplant recipient. Ther Drug Monit 2004;26:453–5
  • Holt DW. Monitoring mycophenolic acid. Ann Clin Biochem 2002;39(Pt 3):173–83
  • Kobashigawa JA, Meiser BM. Review of major clinical trials with mycophenolate mofetil in cardiac transplantation. Transplantation 2005;80(Suppl 2):S235–S243
  • Jain A, Venkataramanan R, Hamad IS, et al. Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus. J Clin Pharmacol 2001;41:268–76
  • Pisupati J, Jain A, Burckart G, et al. Intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid in liver transplant patients. J Clin Pharmacol 2005;45:34–41
  • Van Hest R, Mathot R, Vulto A, et al. Predicting the usefulness of therapeutic drug monitoring of mycophenolic acid: a computer simulation. Ther Drug Monit 2005;27:163–7
  • Krumme B, Wollenberg K, Kirste G, Schollmeyer P. Drug monitoring of mycophenolic acid in the early period after renal transplantation. Transplant Proc 1998;30:1773–4
  • Lu YP, Lin B, Liang MZ, et al. Correlation of mycophenolic acid pharmacokinetic parameters with side effects in Chinese kidney transplant recipients treated with mycophenolate mofetil. Transplant Proc 2004;36:2079–81
  • Pawinski T, Durlik M, Szlaska I, et al. Comparison of mycophenolic acid pharmacokinetic parameters in kidney transplant patients within the first 3 months post-transplant. J Clin Pharm Ther 2006;31:27–34
  • Smak Gregoor PJ, van Gelder T, van Besouw NM, et al. Mycophenolic acid trough levels after kidney transplantation in a cyclosporine-free protocol. Transplant Int 2000;13(Suppl 1): S333–S335
  • Pillans PI, Rigby RJ, Kubler P, et al. A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients. Clin Biochem 2001; 34:77–81
  • Kuypers DR, Vanrenterghem Y, Squifflet JP, et al. Twelve-month evaluation of the clinical pharmacokinetics of total and free mycophenolic acid and its glucuronide metabolites in renal allograft recipients on low dose tacrolimus in combination with mycophenolate mofetil. Ther Drug Monit 2003;25:609–22
  • Hazzan M, Labalette M, Copin MC, et al. Predictive factors of acute rejection after early cyclosporine withdrawal in renal transplant recipients who receive mycophenolate mofetil: results from a prospective, randomized trial. J Am Soc Nephrol 2005;16:2509–16
  • Okamoto M, Wakabayashi Y, Higuchi A, et al. Therapeutic drug monitoring of mycophenolic acid in renal transplant recipients. Transplant Proc 2005;37:859–60
  • Meiser BM, Pfeiffer M, Schmidt D, et al. Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring. J Heart Lung Transplant 1999;18:143–9
  • Yamani MH, Starling RC, Goormastic M, et al. The impact of routine mycophenolate mofetil drug monitoring on the treatment of cardiac allograft rejection. Transplantation 2000;69: 2326–30
  • Gajarski RJ, Crowley DC, Zamberlan MC, Lake KD. Lack of correlation between MMF dose and MPA level in pediatric and young adult cardiac transplant patients: does the MPA level matter? Am J Transplant 2004;4:1495–500
  • Cantin B, Giannetti N, Parekh H, et al. Mycophenolic acid concentrations in long-term heart transplant patients: relationship with calcineurin antagonists and acute rejection. Clin Transplant 2002;16:196–201
  • Hübner GI, Eismann R, Sziegoleit W. Relationship between mycophenolate mofetil side effects and mycophenolic acid plasma trough levels in renal transplant patients. Arzneimittelforschung 2000;50:936–40
  • Mourad M, Malaise J, Chaib Eddour D, et al. Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation. Clin Chem 2001;47:1241–48
  • Mourad M, Malaise J, Chaib Eddour D, et al. Correlation of mycophenolic acid pharmacokinetic parameters with side effects in kidney transplant patients treated with mycophenolate mofetil. Clin Chem 2001;47:88–94
  • Cattaneo D, Gaspari F, Ferrari S, et al. Pharmacokinetics help optimizing mycophenolate mofetil dosing in kidney transplant patients. Clin Transplant 2001;15:402–9
  • Zakliczynski M, Szewczyk M, Zakliczynska H, Zembala M. Clinical application of monitoring mycophenolic acid trough concentration in heart transplant recipients – single center’s experience. Ann Transplant 2005;10:38–45

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.