Pharmacodynamic monitoring of calcineurin inhibition therapy: Principles, performance, and perspectives

Therapeutic Drug Monitoring

Volumn 32, Issue 1, 2010, Pages 3-10

  Van Rossum, Huub H ^a   De Fijter, Johan W ^a   Van Pelt, Johannes ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Calcineurin; Cyclosporin A; Pharmacodynamic monitoring; Tacrolimus; TDM; Transplantation

Indexed keywords

CD28 ANTIGEN; CD3 ANTIBODY; CONCANAVALIN A; CYCLOSPORIN A; IMMUNOSUPPRESSIVE AGENT; IONOMYCIN; MESSENGER RNA; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PHORBOL MYRISTATE; STEROID; TACROLIMUS;

AREA UNDER THE CURVE; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG EFFECT; DRUG MONITORING; DRUG POTENTIATION; ENZYME ACTIVITY; GRAFT REJECTION; HUMAN; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; IN VIVO STUDY; NEPHROTOXICITY; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION;

CALCINEURIN; CYCLOSPORINE; DRUG MONITORING; HUMANS; IMMUNOSUPPRESSIVE AGENTS; ORGAN TRANSPLANTATION; TACROLIMUS;

EID: 75649088107     PISSN: 01634356     EISSN: 15363694     Source Type: Journal    
DOI: 10.1097/FTD.0b013e3181c0eecb     Document Type: Review

References (74)

1. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351:2715-2729.
2. Oellerich M, Armstrong VW. The role of therapeutic drug monitoring in individualizing immunosuppressive drug therapy: recent developments. Ther Drug Monit. 2006;28:720-725.
3. Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007; 357:2562-2575.
4. Hesselink DA, van Gelder T, van Schaik RHN. The pharmacogenetics of calcineurin inhibitors: one step closer toward individualized immuno-suppression? Pharmacogenomics. 2005;6:323-337.
5. Jorgensen KA, Koefoed-Nielsen PB, Karamperis N. Calcineurin phosphatase activity and immunosuppression. A review on the role of calcineurin phosphatase activity and the immunosuppressive effect of cyclosporin A and tacrolimus. Scand J Immunol. 2003;57:93-98.
6. Batiuk TD, Pazderka F, Enns J, et al. Cyclosporine inhibition of calcineurin activity in human-leukocytes in-vivo is rapidly reversible. J Clin Invest. 1995;96:1254-1260
7. vonAhsen N, Helmhold M, Schutz E, et al. Cyclosporin A trough levels correlate with serum lipoproteins and apolipoproteins: Implications for therapeutic drug monitoring of cyclosporin A. Ther Drug Monit. 1997;19: 140-145.
8. Donnenberg VS, Burckart GJ, Griffith BR, et al. P-glycoprotein (P-gp) is upregulated in peripheral T-Cell subsets from solid organ transplant recipients. J Clin Pharmacol. 2001;41:1271-1279.
9. Cattaneo D, Perico N, Remuzzi G. From pharmacokinetics to pharmacogenomics: A new approach to tailor immunosuppressive therapy. Am J Transpl. 2004;4:299-310.
10. Falck P, Asberg A, Guldseth H, et al. Declining intracellular T-lymphocyte concentration of cyclosporine a precedes acute rejection in kidney transplant recipients. Transplantation. 2008;85:179-184.
11. Caruso R, Perico N, Cattaneo D, et al. Whole-blood calcineurin activity is not predicted by cyclosporine blood concentration in renal transplant recipients. Clin Chem. 2001;47:1679-1687.
12. Oellerich M, Barten MJ, Armstrong VW. Biomarkers-the link between therapeutic drug monitoring and pharmacodynamics. Ther Drug Monit. 2006;28:35-38.
13. van Rossum HH, Romijn FPHT, Smit NPM, et al. Everolimus and Sirolimus antagonize tacrolimus based calcineurin inhibition via competition for FK-binding protein 12. Biochem Pharmacol. 2009;77:1203-1212.
14. Bohler T, Nolting J, Kamar N, et al. Validation of immunological biomarkers for the pharmacodynamic monitoring of immunosuppressive drugs in humans. Ther Drug Monit. 2007;29:77-86.
15. Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707-747.
16. Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000; 80:1483-1521.
17. Perrino BA, Wilson AJ, Ellison P, et al. Substrate selectivity and sensitivity to inhibition by FK506 and cyclosporin A of calcineurin heterodimers composed of the alpha or beta catalytic subunit. Eur J Biochem. 2002;269:3540-3548.
18. Bram RJ, Hung DT, Martin PK, et al. Identification of the immunophilins capable of mediating inhibition of signal-transduction by cyclosporine-A and Fk506-roles of calcineurin binding and cellular location. Mol Cell Biol. 1993;13:4760-4769.
19. Crabtree GR. Calcium, calcineurin, and the control of transcription. J Biol Chem. 2001;276:2313-2316.
20. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol. 2005;5:472-484.
21. Morris JC, Waldmann TA. Advances in interleukin 2 receptor targeted treatment. Ann Rheum Dis. 2000;59:109-114.
22. Giese T, Zeier M, Schemmer P, et al. Monitoring of NFAT-REGULATED gene expression in the peripheral blood of allograft recipients: a novel perspective toward individually optimized drug doses of cyclosporine A. Transplantation. 2004;77:339-344.
23. Boehm U, Klamp T, Groot M, et al. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749-795.
24. Shi YF, Liu CH, Roberts AI, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don't know. Cell Res. 2006;16:126-133.
25. Pizarro TT, Malinowska K, Kovacs EJ, et al. Induction of Tnf-alpha and Tnf-beta Gene-expression in rat cardiac transplants during allograft-rejection. Transplantation. 1993;56:399-404.
26. Waldmann TA. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986;232:727-732.
27. Fuleihan R, Ramesh N, Horner A, et al. Cyclosporine-A inhibits Cd40 ligand expression in T-lymphocytes. J Clin Invest. 1994;93:1315-1320.
28. Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003;3:745-756.
29. van Kooten C, Banchereau J. CD40-CD40 ligand. J Leuk Biol. 2000;67: 2-17.
30. Sugamura K, Ishii N, Weinberg AD. Therapeutic targeting of the effector T-cell co-stimulatory molecule OX40. Nat Rev Immunol. 2004;4: 420-431.
31. Gramaglia I, Weinberg AD, Lemon M, et al. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol. 1998;161:6510-6517.
32. Green DR, Droin N, Pinkoski M. Activation-induced cell death in T cells. Immunol Rev. 2003;193:70-81.
33. Koopman G, Degraaff M, Huysmans ACLM, et al. Induction of homotypic T-cell adhesion by triggering of leukocyte function-associated antigen-1-alpha (Cd11A)-differential-effects on resting and activated T-cells. Eur J Immunol. 1992;22:1851-1856.
34. Marzio R, Mauel J, Betz-Corradin S. CD69 and regulation of the immune function. Immunopharmacol Immunotoxicol. 1999;21:565-582.
35. Batista A, Millan J, Mittelbrunn M, et al. Recruitment of transferrin receptor to immunological synapse in response to TCR engagement. J Immunol. 2004;172:6709-6714.
36. Fruman DA, Klee CB, Bierer BE, et al. Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci USA. 1992;89:3686-3690.
37. Koefoed-Nielsen PB, Karamperis N, Jorgensen KA. Validation of the calcineurin phosphatase assay. Clin Chem. 2004;50:2331-2337.
38. Fukudo M, Yano I, Masuda S, et al. Pharmacodynamic analysis of tacrolimus and cyclosporine in living-donor liver transplant patients. Clin Pharmacol Ther. 2005;78:168-181.
39. Sellar KJ, van Rossum HH, Romijn FPHT, et al. Spectrophotometric assay for calcineurin activity in leukocytes isolated from human blood. Anal Biochem. 2006;358:104-110.
40. Kung L, Batiuk TD, Palomo-Pinon S, et al. Tissue distribution of calcineurin and its sensitivity to inhibition by cyclosporine. Am J Transpl. 2001;1:325-333.
41. Kung L, Halloran PF. Immunophilins may limit calcineurin inhibition by cyclosporine and tacrolimus at high drug concentrations. Transplantation. 2000;70:327-335.
42. Vethe NT, Bergan S. Determination of inosine monophosphate de-hydrogenase activity in human CD4+cells isolated from whole blood during mycophenolic acid therapy. Ther Drug Monit. 2006;28:608-613.
43. van Rossum HH, Romijn FPHT, Sellar KJ, et al. Variation in leukocyte subset concentrations affects calcineurin activity measurement: implications for pharmacodynamic monitoring strategies. Clin Chem. 2008; 54:517-524.
44. Yano I. Pharmacodynamic monitoring of calcineurin phosphatase activity in transplant recipients treated with calcineurin inhibitors. Drug Metab Pharmacokinet. 2008;23:150-157.
45. Sommerer C, Giese T, Meuer S, et al. Pharmacodynamic monitoring of calcineurin inhibitor therapy: Is there a clinical benefit? Nephrol Dial Transpl. 2009;24:21-27.
46. Halloran PF, Helms LM, Kung L, et al. The temporal profile of calcineurin inhibition by cyclosporine in vivo. Transplantation. 1999;68:1356-1361.
47. Koefoed-Nielsen PB, Gesualdo MB, Poulsen JH, et al. Blood tacrolimus levels and calcineurin phosphatase activity early after renal transplantation. Am J Transpl. 2002;2:173-178.
48. Koefoed-Nielsen PB, Karamperis N, Jorgensen KA. Comparison of the temporal profile of calcineurin inhibition by cyclosporine and tacrolimus in renal transplant patients. Transpl Proc. 2005;37:1736-1738.
49. Pazderka F, Enns J, Batiuk TD, et al. The functional consequences of partial calcineurin inhibition in human peripheral blood mononuclear leucocytes. Transpl Immunol. 1996;4:23-31.
50. Batiuk TD, Pazderka F, Enns J, et al. Cyclosporine inhibition of leukocyte calcineurin is much less in whole blood than in culture medium. Transplantation. 1996;61:158-161.
51. Sanquer S, Schwarzinger M, Maury S, et al. Calcineurin activity as a functional index of immunosuppression after allogeneic stem-cell transplantation. Transplantation. 2004;77:854-858.
52. Pai SY, Fruman DA, Leong T, et al. Inhibition of calcineurin phosphatase-activity in adult bone-marrow transplant patients treated with cyclospor-ine-A. Blood. 1994;84:3974-3979.
53. Brunet M, Crespo M, Millan O, et al. Pharmacokinetics and pharmacodynamics in renal transplant recipients under treatment with cyclosporine and myfortic. Transpl Proc. 2007;39:2160-2162.
54. Rogers AJ, Yoshimura N, Kerman RH, et al. Immunopharmacodynamic evaluation of cyclosporine-treated renal-allograft recipients. Transplantation. 1984;38:657-664.
55. Yoshimura N, Kahan BD. Pharmacodynamic assessment of the in vivo cyclosporine effect on interleukin-2 production by lymphocytes in kidney-transplant recipients. Transplantation. 1985;40:661-666.
56. Barten MJ, Gummert JF, van Gelder T, et al. Flow cytometric quantitation of calcium-dependent and-independent mitogen-stimulation of T cell functions in whole blood: inhibition by immunosuppressive drugs in vitro. J Immunol Methods. 2001;253:95-112.
57. Hartel C, Fricke L, Schumacher N, et al. Delayed cytokine mRNA expression kinetics after T-lymphocyte costimulation: a quantitative measure of the efficacy of cyclosporin A-based immunosuppression. Clin Chem. 2002;48:2225-2231.
58. Diehn M, Alizadeh AA, Rando OJ, et al. Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc Natl Acad Sci USA. 2002;99:11796-11801.
59. El-Safa EA, Fredericks S, MacPhee I, et al. Paradoxical response to tacrolimus assessed by interleukin-2 gene expression. Transpl Proc. 2006; 38:3327-3330.
60. Giese T, Zeier M, Schemmer P, et al. Monitoring of NFAT-REGULATED gene expression in the peripheral blood of allograft recipients: A novel perspective toward individually optimized drug doses of cyclosporine A. Transplantation. 2004;77:339-344.
61. Sommerer C, Konstandin M, Dengler T, et al. Pharmacodynamic monitoring of cyclosporine A in renal allograft recipients shows a quantitative relationship between immunosuppression and the occurrence of recurrent infections and malignancies. Transplantation. 2006;82: 1280-1285.
62. Barten MJ, Tarnok A, Garbade J, et al. Pharmacodynamics of T-cell function for monitoring immunosuppression. Cell Prolif. 2007;40:50-63.
63. Boleslawski E, Conti F, Sanquer S, et al. Defective inhibition of peripheral CD8+T cell IL-2 production by anti-calcineurin drugs during acute liver allograft rejection. Transplantation. 2004;77:1815-1820.
64. Barten MJ, Rahmel A, Boldt A, et al. Pharmacodynamic monitoring of the immunosuppressive therapy in patients after heart transplantation: whole blood flow cytometric analysis of lymphocyte function. Comput Biol Med. 2007;37:1367-1373.
65. van Rossum HH, Romijn FPHTM, Lentz-Ljuboje R, et al. Monitoring of calcineurin activity under controlled systemic cyclosporine exposure after renal transplantation. Ned Tijdschr Klin Chem Labgeneesk. 2007; 32:272-273.
66. Fukudo M, Yano I, Masuda S, et al. Distinct inhibitory effects of tacrolimus and cyclosporin A on calcineurin phosphatase activity. J Pharmacol Exp Ther. 2005;312:816-825.
67. Millan O, Brunet M, Campistol JM, et al. Pharmacodynamic approach to immunosuppressive therapies using calcineurin inhibitors and mycophe-nolate mofetil. Clin Chem. 2003;49:18911899.
68. Blanchet B, Hulin A, Duvoux C, et al. Determination of serine/threonine protein phosphatase type 2B PP2B in lymphocytes by HPLC. Anal Biochem. 2003;312:1-6.
69. Giese T, Zeier M, Meuer S. Analysis of NFAT-regulated gene expression in vivo: a novel perspective for optimal individualized doses of calcineurin inhibitors. Nephrol Dial Transpl. 2004;19:55-60.
70. Hartel C, Schumacher N, Fricke L, et al. Sensitivity of whole-blood T lymphocytes in individual patients to tacrolimus (FK 506): impact of interleukin-2 mRNA expression as surrogate measure of immunosup-pressive effect. Clin Chem. 2004;50:141-151.
71. Stein CM, Murray JJ, Wood AJJ. Inhibition of stimulated interleukin-2 production in whole blood: a practical measure of cyclosporine effect. Clin Chem. 1999;45:1477-1484.
72. Hodge G, Hodge S, Reynolds P, et al. Intracellular cytokines in blood T cells in lung transplant patients-a more relevant indicator of immuno-suppression than drug levels. Clin Exp Immunol. 2005;139:159-164.
73. Stalder M, Birsan T, Holm B, et al. Quantification of immunosuppression by flow cytometry in stable renal transplant recipients. Ther Drug Monit. 2003;25:22-27.
74. Barten MJ, Dhein S, Chang H, et al. Assessment of immuno suppressive drug interactions: inhibition of lymphocyte function in peripheral human blood. J Immunol Methods. 2003;283:99-114.