The rationale for and limitations of therapeutic drug monitoring for mycophenolate mofetil in transplantation

Transplantation

Volumn 80, Issue SUPPL. 2, 2005, Pages

  Van Gelder, Teun ^a   Shaw, Leslie M ^b  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Mycophenolate mofetil; Mycophenolic acid; Therapeutic drug monitoring; Transplantation

Indexed keywords

ACICLOVIR; CALCINEURIN INHIBITOR; COLESTYRAMINE; CYCLOSPORIN; DRUG METABOLITE; GANCICLOVIR; INOSINATE DEHYDROGENASE; MYCOPHENOLIC ACID; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; TACROLIMUS;

ACUTE GRAFT REJECTION; ANEMIA; AREA UNDER THE CURVE; BLOOD TOXICITY; CLINICAL TRIAL; CORRELATION ANALYSIS; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DETERMINATION; DRUG HALF LIFE; DRUG MONITORING; DRUG PROTEIN BINDING; ENZYME ACTIVITY; ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE; FOOD DRUG INTERACTION; GASTROINTESTINAL SYMPTOM; HEART TRANSPLANTATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; LEUKOPENIA; NONHUMAN; PREOPERATIVE EVALUATION; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; TREATMENT OUTCOME;

ADULT; CHILD; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG INTERACTIONS; DRUG MONITORING; HEART TRANSPLANTATION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; MYCOPHENOLIC ACID; TREATMENT OUTCOME;

EID: 27644434992     PISSN: 00411337     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.tp.0000186380.61251.fc     Document Type: Review

References (87)

1. Sollinger HW, Deierhoi MH, Belzer FO, et al. RS-61443-a phase I clinical trial and pilot rescue study. Transplantation 1992; 53: 428.
2. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 1995; 345: 1321.
3. Sollinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 1995; 60: 225.
4. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61: 1029.
5. CellCept [package insert]. Nutley, NJ: Roche Laboratories, Inc.; 2004.
6. Meier-Kriesche H-U, Steffen BJ, Hochberg AM, et al. Long-term use of mycophenolate mofetil is associated with a reduction in the incidence and risk of late rejection. Am J Transplant 2003; 3: 68.
7. Meier-Kriesche H-U, 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.
8. Shaw LM, Kaplan B, DeNofrio D, et al. Pharmacokinetics and concentration-control investigations of mycophenolic acid in adults after transplantation. Ther Drug Monit 2000; 22: 14.
9. Bennett WM. Immunosuppression with mycophenolic acid: one size does not fit all. J Am Soc Nephrol 2003; 14: 2414.
10. Hale MD, Nicholls AJ, Bullingham RE, et al. The pharmacokinetic- pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Pharmacol Ther 1998; 64: 672.
11. Cattaneo D, Gaspari F, Ferrari S, et al. Pharmacokinetics help optimizing mycophenolate mofetil dosing in kidney transplant patients. Clin Transplant 2001; 15: 402.
12. Filler G, Zimmering M, Mai I. Pharmacokinetics of mycophenolate mofetil are influenced by concomitant immunosuppression. Pediatr Nephrol 2000; 14: 100.
13. 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.
14. Cho E, Han D, Kim S, et al. Pharmacokinetic study of mycophenolic acid in Korean kidney transplant patients. J Clin Pharmacol 2004; 44: 743.
15. Schweitzer EJ, Yoon S, Fink J, et al. Mycophenolate mofetil reduces the risk of acute rejection less in African-American than in Caucasian kidney recipients. Transplantation 1998; 65: 242.
16. Neylan JF. Immunosuppressive therapy in high-risk transplant patients: dose-dependent efficacy of mycophenolate mofetil in African-American renal allograft recipients. U.S. Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 1997; 64: 1277.
17. 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.
18. 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.
19. Shaw LM, Mick R, Nowak I, et al. Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function. J Clin Pharmacol 1998; 38: 268.
20. Sollinger HW. Mycophenolates in transplantation. Clin Transplant 2004; 18: 485.
21. Myfortic [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; 2004.
22. Fulton B, Markham A. Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 1996; 51: 278.
23. van Hest R, Mathot R, Vulto A, et al. Mycophenolic acid in diabetic renal transplant patients - pharmacokinetics and application of a limited sampling strategy. Ther Drug Monit 2004; 26: 620.
24. Mudge DW, Atcheson B, Taylor PJ, et al. The effect of oral iron administration on mycophenolate mofetil absorption in renal transplant recipients: a randomized, controlled trial. Transplantation 2004; 77: 206.
25. Bullingham R, Monroe S, Nicholls A, Hale M. Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration. J Clin Pharmacol 1996; 36: 315.
26. Bullingham RE, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. Clin Pharmacokinet 1998; 34: 429.
27. Smak Gregoor PJ, van Gelder T, Hesse CJ, et al. Mycophenolic acid plasma concentrations in kidney allograft recipients with or without cyclosporin: a cross-sectional study. Nephrol Dial Transplant 1999; 14: 706.
28. 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.
29. Shipkova M, Armstrong VW, Kuypers D, et al. Effect of cyclosporine withdrawal on mycophenolic acid pharmacokinetics in kidney transplant recipients with deteriorating renal function: preliminary report. Ther Drug Monit 2001; 23: 717.
30. van Gelder T, Klupp J, Barten MJ, et al. Comparison of the effects of tacrolimus and cyclosporine on the pharmacokinetics of mycophenolic acid. Ther Drug Monit 2001; 23: 119.
31. Deters M, Kirchner G, Koal T, et al. Influence of cyclosporine on the serum concentration and biliary excretion of mycophenolic acid and 7-O-mycophenolic acid glucuronide. Ther Drug Monit 2005; 27: 132.
32. Kobayashi M, Saitoh H, Tadano K, et al. Cyclosporin A, but not tacrolimus, inhibits the biliary excretion of mycophenolic acid glucuronide possibly mediated by multidrug resistance-associated protein 2 in rats. J Pharmacol Exp Ther 2004; 309: 1029.
33. 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.
34. Paulusma CC, Bosma PJ, Zaman GJ, et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 1996; 271: 1126.
35. Gotoh Y, Suzuki H, Kinoshita S, et al. Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats. J Pharmacol Exp Ther 2000; 292: 433.
36. Zucker K, Rosen A, Tsaroucha A, et al. Augmentation of mycophenolate mofetil pharmacokinetics in renal transplant patients receiving Prograf and CellCept in combination therapy. Transplant Proc 1997; 29: 334.
37. Zucker K, Rosen A, Tsaroucha A, et al. Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings. Transpl Immunol 1997; 5: 225.
38. Kuriata-Kordek M, Boratynska M, Falkiewicz K, et al. The influence of calcineurin inhibitors on mycophenolic acid pharmacokinetics. Transplant Proc 2003; 35: 2369.
39. Zucker K, Tsaroucha A, Olson L, et al. Evidence that tacrolimus augments the bioavailability of mycophenolate mofetil through the inhibition of mycophenolic acid glucuronidation. Ther Drug Monit 1999; 21: 35.
40. Flechner SM, Goldfarb D, Modlin C, et al. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 2002; 74: 1070.
41. Cattaneo D, Perico N, Gaspari F, et al. Glucocorticoids interfere with mycophenolate mofetil bioavailability in kidney transplantation. Kidney Int 2002; 62: 1060.
42. Nowak I, Shaw LM. Mycophenolic acid binding to human serum albumin: characterization and relation to pharmacodynamics. Clin Chem 1995; 41: 1011.
43. 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.
44. 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.
45. Touw DJ, Neef C, Thomson AH, Vinks AA. Cost-effectiveness of therapeutic drug monitoring: a systematic review. Ther Drug Monit 2005; 27: 10.
46. Srinivas TR, Meier-Kriesche H-U, Kaplan B. Pharmacokinetic principles of immunosuppressive drugs. Am J Transplant 2005; 5: 207.
47. Johnston A, Holt DW. Immunosuppressant drugs-the role of therapeutic drug monitoring. Br J Clin Pharmacol 2001; 52 (Suppl 1): 61S.
48. Takahashi K, Ochiai T, Uchida K, et al. Pilot study of mycophenolate mofetil (RS-61443) in the prevention of acute rejection following renal transplantation in Japanese patients. RS-61443 Investigation Committee-Japan. Transplant Proc 1995; 27: 1421.
49. Nicholls AJ. Opportunities for therapeutic monitoring of mycophenolate mofetil dose in renal transplantation suggested by the pharmacokinetic/ pharmacodynamic relationship for mycophenolic acid and suppression of rejection. Clin Biochem 1998; 31: 329.
50. Atcheson BA, Taylor PJ, Mudge DW, et al. Mycophenolic acid pharmacokinetics and related outcomes early after renal transplant. Br J Clin Pharmacol 2005; 59: 271.
51. 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.
52. 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.
53. 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.
54. 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.
55. 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.
56. 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.
57. Oellerich M, Shipkova M, Schutz E, et al. Pharmacokinetic and metabolic investigations of mycophenolic acid in pediatric patients after renal transplantation: implications for therapeutic drug monitoring. German Study Group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients. Ther Drug Monit 2000; 22: 20.
58. Weber LT, Lamersdorf T, Shipkova M, et al. Area under the plasma concentration-time curve for total, but not for free, mycophenolic acid increases in the stable phase after renal transplantation: a longitudinal study in pediatric patients. German Study Group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients. Ther Drug Monit 1999; 21: 498.
59. Shipkova M, Armstrong VW, Oellerich M, Wieland E. Acyl glucuronide drug metabolites: toxicological and analytical implications. Ther Drug Monit 2003; 25: 1.
60. DeNofrio D, Loh E, Kao A, et al. Mycophenolic acid concentrations are associated with cardiac allograft rejection. J Heart Lung Transplant 2000; 19: 1071.
61. 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.
62. Goldberg L, DeNofrio D, Nawrocki A, et al. Early mycophenolic acid pharmacokinetics predict acute rejection in the first three months following heart transplantation [Abstract]. Am J Transplant 2003; 3: 385.
63. 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.
64. 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.
65. Shaw LM, Nicholls A, Hale M, et al. Therapeutic monitoring of mycophenolic acid. A consensus panel report. Clin Biochem 1998; 31: 317.
66. 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.
67. Filler G. Abbreviated mycophenolic acid AUC from C0, C1, C2, and C4 is preferable in children after renal transplantation on mycophenolate mofetil and tacrolimus therapy. Transpl Int 2004; 17: 120.
68. Willis C, Taylor PJ, Salm P, et al. Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients. Ther Drug Monit 2000; 22: 549.
69. Le Guellec C, Buchler M, Giraudeau B, et al. Simultaneous estimation of cyclosporin and mycophenolic acid areas under the curve in stable renal transplant patients using a limited sampling strategy. Eur J Clin Pharmacol 2002; 57: 805.
70. Kuypers DR. Immunosuppressive drug monitoring - what to use in clinical practice today to improve renal graft outcome. Transpl Int 2005; 18: 140.
71. 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.
72. Knoll GA, MacDonald I, Khan A, Van Walraven C. Mycophenolate mofetil dose reduction and the risk of acute rejection after renal transplantation. J Am Soc Nephrol 2003; 14: 2381.
73. Holt DW. Monitoring mycophenolic acid. Ann Clin Biochem 2002; 39: 173.
74. Morris RG. Immunosuppressant drug monitoring: Is the laboratory meeting clinical expectations? Ann Pharmacother 2005; 39: 119.
75. Beal JL, Jones CE, Taylor PJ, Tett SE. Evaluation of an immunoassay (EMIT) for mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatography assay. Ther Drug Monit 1998; 20: 685.
76. Schutz E, Shipkova M, Armstrong VW, et al. Identification of a pharmacologically active metabolite of mycophenolic acid in plasma of transplant recipients treated with mycophenolate mofetil. Clin Chem 1999; 45: 419.
77. 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.
78. Weber LT, Shipkova M, Armstrong VW, et al. Comparison of the EMIT immunoassay with HPLC for therapeutic drug monitoring of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy. Clin Chem 2002; 48: 517.
79. Holt DW, Armstrong VW, Griesmacher A, et al. International Federation of Clinical Chemistry/International Association of Therapeutic Drug Monitoring and Clinical Toxicology working group on immunosuppressive drug monitoring. Ther Drug Monit 2002; 24: 59.
80. Dorn A, Mountain L, Phillips M, et al. Roche diagnostics automated clinical chemistry analyzer enzyme/receptor assay for total and free mycophenolic acid measurement in transplant patient samples. Clin Chem 2004; 50 (Suppl): A134.
81. Kaplan B, Gruber SA, Nallamathou R, et al. Decreased protein binding of mycophenolic acid associated with leukopenia in a pancreas transplant recipient with renal failure. Transplantation 1998; 65: 1127.
82. Atcheson BA, Taylor PJ, Kirkpatrick CM, et al. Free mycophenolic acid should be monitored in renal transplant recipients with hypoalbuminemia. Ther Drug Monit 2004; 26: 284.
83. Mourad M, Wallemacq P, Konig J, et al. Therapeutic monitoring of mycophenolate mofetil in organ transplant recipients: Is it necessary? Clin Pharmacokinet 2002; 41: 319.
84. Glander P, Hambach P, Braun KP, et al. Effect of mycophenolate mofetil on IMP dehydrogenase after the first dose and after long-term treatment in renal transplant recipients. Int J Clin Pharmacol Ther 2003; 41: 470.
85. Budde K, Glander P, Bauer S, et al. Pharmacodynamic monitoring of mycophenolate mofetil. Clin Chem Lab Med 2000; 38: 1213.
86. 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.
87. van Gelder T. Mycophenolate mofetil: How to further improve using an already successful drug? Am J Transplant 2005; 5: 199.