Focus on mTOR inhibitors and tacrolimus in renal transplantation: Pharmacokinetics, exposure-response relationships, and clinical outcomes

Transplant Immunology

Volumn 31, Issue 1, 2014, Pages 22-32

  Shihab, Fuad ^a   Christians, Uwe ^b   Smith, Lonnie ^c   Wellen, Jason R ^d   Kaplan, Bruce ^e  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF UTAH   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

Author keywords

Calcineurin inhibitors; MTOR inhibitors; Pharmacokinetics; Renal transplantation; Tacrolimus; Therapeutic drug monitoring

Indexed keywords

BASILIXIMAB; CORTICOSTEROID; CYCLOSPORIN A; EVEROLIMUS; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RAPAMYCIN; STEROID; TACROLIMUS; CALCINEURIN INHIBITOR; IMMUNOSUPPRESSIVE AGENT; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ANEMIA; AREA UNDER THE CURVE; ARTHRALGIA; CREATININE BLOOD LEVEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG METABOLISM; DRUG MONITORING; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EDEMA; GRAFT SURVIVAL; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY FUNCTION; KIDNEY TRANSPLANTATION; LOADING DRUG DOSE; LOW DRUG DOSE; NEPHROTOXICITY; PERIPHERAL EDEMA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; SURVIVAL RATE; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS;

CALCINEURIN INHIBITORS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; SIROLIMUS; TACROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84903786099     PISSN: 09663274     EISSN: 18785492     Source Type: Journal    
DOI: 10.1016/j.trim.2014.05.002     Document Type: Review

References (61)

1. Salvadori M., Bertoni E. Is it time to give up with calcineurin inhibitors in kidney transplantation?. World J Transplant 2013, 3:7-25.
2. Knops N., Levtchenko E., van den Heuvel B., Kuypers D. From gut to kidney: transporting and metabolizing calcineurin-inhibitors in solid organ transplantation. Int J Pharm 2013, 452:14-35.
3. Johnson R.W., Kreis H., Oberbauer R., Brattström C., Claesson K., Eris J. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001, 72:777-786.
4. Nankivell B.J., Borrows R.J., Fung C.L., O'Connell P.J., Allen R.D., Chapman J.R. The natural history of chronic allograft nephropathy. N Engl J Med 2003, 349:2326-2333.
5. Halloran P.F., Reeve J.P., Pereira A.B., Hidalgo L.G., Famulski K.S. Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: new insights from the Genome Canada studies of kidney transplant biopsies. Kidney Int 2014, 85:258-264.
6. Augustine J.J., Hricik D.E. Minimization of immunosuppression in kidney transplantation. Curr Opin Nephrol Hypertens 2007, 16:535-541.
7. Schuler W., Sedrani R., Cottens S., Haberlin B., Schulz M., Schuurman H.J., et al. SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo. Transplantation 1997, 64:36-42.
8. Schuurman H.J., Cottens S., Fuchs S., Joergensen J., Meerloo T., Sedrani R., et al. SDZ RAD, a new rapamycin derivative: synergism with cyclosporine. Transplantation 1997, 64:32-35.
9. Sehgal S.N. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem 1998, 31:335-340.
10. Nashan B., Curtis J., Ponticelli C., Mourad G., Jaffe J., Haas T., et al. Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study. Transplantation 2004, 78:1332-1340.
11. Baboolal K. A phase III prospective, randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients. Transplantation 2003, 75:1404-1408.
12. Tedesco Silva H., Cibrik D., Johnston T., Lackova E., Mange K., Panis C., et al. Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal-transplant recipients. Am J Transplant 2010, 10:1401-1413.
13. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR) OPTN/SRTR 2010 Annual Data Report 2011, Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation, Rockville, MD, [Available at http://www.srtr.org/annual_reports/2010/. Accessed August 1, 2012].
14. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009, 9(Suppl. 3):S1-S157.
15. Schiff J., Cole E., Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clin J Am Soc Nephrol 2007, 2:374-384.
16. Wallemacq P., Armstrong V.W., Brunet M., Haufroid V., Holt D.W., Johnston A., et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference. Ther Drug Monit 2009, 31:139-152.
17. Kuypers D.R., Le Meur Y., Cantarovich M., Tredger M.J., Tett S.E., Cattaneo D., et al. Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation. Clin J Am Soc Nephrol 2010, 5:341-358.
18. Kirchner G.I., Meier-Wiedenbach I., Manns M.P. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet 2004, 43:83-95.
19. Salvadori M., Bertoni E. Long-term outcome of everolimus treatment in transplant patients. Transpl Res Risk Manag 2011, 3:77-90.
20. MacDonald A., Scarola J., Burke J.T., Zimmerman J.J. Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus. Clin Ther 2000, 22:B101-B121. [Suppl. B].
21. Mahalati K., Kahan B.D. Clinical pharmacokinetics of sirolimus. Clin Pharmacokinet 2001, 40:573-585.
22. Kahan B.D., Napoli K.L., Kelly P.A., Podbielski J., Hussein I., Urbauer D.L., et al. Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity. Clin Transplant 2000, 14:97-109.
23. Kovarik J.M., Kahan B.D., Kaplan B., Lorber M., Winkler M., Rouilly M., et al. Longitudinal assessment of everolimus in de novo renal transplant recipients over the first post-transplant year: pharmacokinetics, exposure-response relationships, and influence on cyclosporine. Clin Pharmacol Ther 2001, 69:48-56.
24. Kahan B.D., Napoli K.L., Podbielski J., Hussein I., Katz S.H., Van Buren C.T. Therapeutic drug monitoring of sirolimus for optimal renal transplant outcomes. Transplant Proc 2001, 33:1278.
25. Zortress (everolimus) tablets for oral use [prescribing information] 2013, Novartis Pharmaceuticals Corporation, East Hanover, NJ.
26. Kovarik J.M., Kaplan B., Silva H.T., Kahan B.D., Dantal J., McMahon L., et al. Pharmacokinetics of an everolimus-cyclosporine immunosuppressive regimen over the first 6months after kidney transplantation. Am J Transplant 2003, 3:606-613.
27. Favi E., Spagnoletti G., Gargiulo A., Salerno M.P., Romagnoli J., Citterio F. Once daily everolimus is safe and effective in de novo renal transplant recipients: six-month results of a pilot study. Transplant Proc 2010, 42:1308-1311.
28. Spagnoletti G., Favi E., Gargiulo A., Salerno M.P., Citterio F. Once-a-day administration of everolimus is safe in de novo renal transplant recipients: 1-year results of a pilot study. Transplant Proc 2011, 43:1010-1012.
29. Carmellini M., Collini A., Ruggieri G., Bernini M. Conversion of stable kidney transplant recipients from a twice-daily to once-daily everolimus regimen. Transplant Proc 2010, 42:1312-1313.
30. Dunn C., Croom K.F. Everolimus: a review of its use in renal and cardiac transplantation. Drugs 2006, 66:547-570.
31. Melancon K., Mulgaonkar S.P., Delcoro C., Wiland A., McCague K., Shihab F.S. Outcomes in ethnic minority renal transplant recipients receiving everolimus versus mycophenolate: comparative risk assessment results from a pooled analysis. Transplantation 2013, 96:1073-1081.
32. Prograf (tacrolimus) capsules and injection [prescribing information] 2012, Astellas Pharma US, Inc., Northbrook, IL.
33. Kovarik J.M., Curtis J.J., Hricik D.E., Pescovitz M.D., Scantlebury V., Vasquez A. Differential pharmacokinetic interaction of tacrolimus and cyclosporine on everolimus. Transplant Proc 2006, 38:3456-3458.
34. Brandhorst G., Tenderich G., Zittermann A., Oezpeker C., Koerfer R., Oellerich M., et al. Everolimus exposure in cardiac transplant recipients is influenced by concomitant calcineurin inhibitor. Ther Drug Monit 2008, 30:113-116.
35. Chan L., Hartmann E., Cibrik D., Cooper M., Shaw L.M. Optimal everolimus concentration is associated with risk reduction for acute rejection in de novo renal transplant recipients. Transplantation 2010, 90:31-37.
36. Pascual J., del Castillo D., Cabello M., Pallardó L., Grinyó J.M., Fernández A.M., et al. Interaction between everolimus and tacrolimus in renal transplant recipients: a pharmacokinetic controlled trial. Transplantation 2010, 89:994-1000.
37. Park S.I., Felipe C.R., Pinheiro-Machado P.G., Garcia R., Fernandes F.B., Casarini D.E., et al. Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus. Fundam Clin Pharmacol 2009, 23:137-145.
38. Baldan N., Rigotti P., Furian L., Margani G., Ekser B., Frison L., et al. Co-administration of sirolimus alters tacrolimus pharmacokinetics in a dose-dependent manner in adult renal transplant recipients. Pharmacol Res 2006, 54:181-185.
39. Kuypers D.R., Claes K., Evenepoel P., Maes B., Vanrenterghem Y. Long-term pharmacokinetic study of the novel combination of tacrolimus and sirolimus in de novo renal allograft recipients. Ther Drug Monit 2003, 25:447-451.
40. Wu F.L., Tsai M.K., Chen R.R., Sun S.W., Huang J.D., Hu R.H., et al. Effects of calcineurin inhibitors on sirolimus pharmacokinetics during staggered administration in renal transplant recipients. Pharmacotherapy 2005, 25:646-653.
41. Lorber M.I., Ponticelli C., Whelchel J., Mayer H.W., Kovarik J., Li Y., et al. Therapeutic drug monitoring for everolimus in kidney transplantation using 12-month exposure, efficacy, and safety data. Clin Transplant 2005, 19:145-152.
42. Kovarik J.M., Kaplan B., Tedesco Silva H., Kahan B.D., Dantal J., Vitko S., et al. Exposure-response relationships for everolimus in de novo kidney transplantation: defining a therapeutic range. Transplantation 2002, 73:920-925.
43. Kovarik J.M., Tedesco H., Pascual J., Civati G., Bizot M.N., Geissler J., et al. Everolimus therapeutic concentration range defined from a prospective trial with reduced-exposure cyclosporine in de novo kidney transplantation. Ther Drug Monit 2004, 26:499-505.
44. Ciancio G., Burke G.W., Gaynor J.J., Mattiazzi A., Roth D., Kupin W., et al. A randomized long-term trial of tacrolimus and sirolimus versus tacrolimus and mycophenolate mofetil versus cyclosporine (NEORAL) and sirolimus in renal transplantation. I. Drug interactions and rejection at one year. Transplantation 2004, 77:244-251.
45. Chan L., Greenstein S., Hardy M.A., Hartmann E., Bunnapradist S., Cibrik D., et al. Multicenter, randomized study of the use of everolimus with tacrolimus after renal transplantation demonstrates its effectiveness. Transplantation 2008, 85:821-826.
46. Langer R.M., Hené R., Vitko S., Christiaans M., Tedesco-Silva H., Ciechanowski K., et al. Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation. Transpl Int 2012, 25:592-602.
47. Russ G.R., Campbell S., Chadban S., Eris J., O'Connell P., Pussell B., et al. Reduced and standard target concentration tacrolimus with sirolimus in renal allograft recipients. Transplant Proc 2003, 35:115S-117S.
48. Lo A., Egidi M.F., Gaber L.W., Amiri H.S., Vera S., Nezakatgoo N., et al. Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation. Transplantation 2004, 77:1228-1235.
49. Lo A., Egidi M.F., Gaber L.W., Shokouh-Amiri M.H., Nazakatgoo N., Fisher J.S., et al. Observations regarding the use of sirolimus and tacrolimus in high-risk cadaveric renal transplantation. Clin Transplant 2004, 18:53-61.
50. Hamdy A.F., El-Agroudy A.E., Bakr M.A., Mostafa A., El-Baz M., El-Shahawy E., et al. Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation. Am J Transplant 2005, 5:2531-2538.
51. Ciancio G., Burke G.W., Gaynor J.J., Ruiz P., Roth D., Kupin W., et al. A randomized long-term trial of tacrolimus/sirolimus versus tacrolimus/mycophenolate versus cyclosporine/sirolimus in renal transplantation: three-year analysis. Transplantation 2006, 81:845-852.
52. Guerra G., Ciancio G., Gaynor J.J., Zarak A., Brown R., Hanson L., et al. Randomized trial of immunosuppressive regimens in renal transplantation. J Am Soc Nephrol 2011, 22:1758-1768.
53. Chhabra D., Skaro A.I., Leventhal J.R., Dalal P., Shah G., Wang E., et al. Long-term kidney allograft function and survival in prednisone-free regimens: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus. Clin J Am Soc Nephrol 2012, 7:504-512.
54. Mabasa V.H., Ensom M.H. The role of therapeutic monitoring of everolimus in solid organ transplantation. Ther Drug Monit 2005, 27:666-676.
55. Stenton S.B., Partovi N., Ensom M.H. Sirolimus: the evidence for clinical pharmacokinetic monitoring. Clin Pharmacokinet 2005, 44:769-786.
56. Pieri M., Miraglia N., Polichetti G., Tarantino G., Acampora A., Capone D. Analytical and pharmacological aspects of therapeutic drug monitoring of mTOR inhibitors. Curr Drug Metab 2011, 12:253-267.
57. Peddi V.R., Wiseman A., Chavin K., Slakey D. Review of combination therapy with mTOR inhibitors and tacrolimus minimization after transplantation. Transplant Rev (Orlando) 2013, 27:97-107.
58. Campistol J.M., Cockwell P., Diekmann F., Donati D., Guirado L., Herlenius G., et al. Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation. Transpl Int 2009, 22:681-687.
59. Wiseman A.C., McCague K., Kim Y., Geissler F., Cooper M. The effect of everolimus versus mycophenolate upon proteinuria following kidney transplant and relationship to graft outcomes. Am J Transplant 2013, 13:442-449.
60. Rodrigo E., Fernandez-Fresnedo G., Valero R., Ruiz J.C., Piñera C., Palomar R., et al. New-onset diabetes after kidney transplantation: risk factors. J Am Soc Nephrol 2006, 17:S291-S295.
61. Dantal J., Berthoux F., Moal M.C., Rostaing L., Legendre C., Genin R., et al. Efficacy and safety of de novo or early everolimus with low cyclosporine in deceased-donor kidney transplant recipients at specified risk of delayed graft function: 12-month results of a randomized, multicenter trial. Transpl Int 2010, 23:1084-1093.