Sirolimus, a new, potent immunosuppressive agent

Pharmacotherapy

Volumn 17, Issue 6, 1997, Pages 1148-1156

  Kelly, Patrick A ^a   Gruber, Scott A ^a   Behbod, Fariba ^a   Kahan, Barry D ^a  

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOSPORIN A; IMMUNOSUPPRESSIVE AGENT; RAPAMYCIN;

AREA UNDER THE CURVE; CLINICAL TRIAL; DRUG MECHANISM; DRUG MONITORING; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTRIGLYCERIDEMIA; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY GRAFT REJECTION; KIDNEY TRANSPLANTATION; LEUKOPENIA; NONHUMAN; POSTOPERATIVE COMPLICATION; REVIEW; THROMBOCYTOPENIA;

ANIMALS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; POLYENES; SIROLIMUS; TRANSPLANTATION IMMUNOLOGY;

EID: 0030707884     PISSN: 02770008     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (74)

1. Sehgal SN, Baker H, Vezina C. Rapamycin (AY-22,989), a new antifungal antibiotic. Fermentation, isolation and characterization. J Antibiot 1975;28:727-32.
2. Venzia C, Kudelski A, Sehgal SN. Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot 1975;28:712-26.
3. Martel RR, Klicius J, Galet S. Inhibition of the immune response by rapamycin, a new antifungal antibiotic. Can J Physiol Pharmacol 1977;55:48-51.
4. Bierer BE, Mattila PS, Standaert RF, et al. Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin. Proc Natl Acad Sci USA 1990;87:9231-5.
5. Fruman DA, Burakoff SJ, Bierer BE. Molecular actions of cyclosporine A, FK506, and rapamycin. In: Thomson AW, Strazl TE, eds. Immunosuppressive drugs: development in antirejection therapy. London: Edward Arnold, 1994:15-35.
6. Schreiber SL. Chemistry and biology of the immunophilins and their immunosuppressive ligands. Science 1991; 251(4991):283-7.
7. Galat A, Lane WS, Standaert RF, Schreiber SL. A rapamycin-selective 25-kDa immunophilin. Biochemistry 1992;31: 2427-34.
8. Jin YJ, Burakoff SJ, Bierer BE. Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25. J Biol Chem 1992;267:10942-5.
9. Timerman AP, Ogunbumni E, Freund E, Wiederrecht G, Marks AR, Fleischer S. The calcium release channel of sarcoplasmic reticulum is modulated by FK-506 binding protein. Dissociation and reconstitution of FKBP-12 to the calcium release channel of skeletal muscle sarcoplasmic reticulum. J Biol Chem 1993;268:22992-9.
10. Cameron AM, Steiner JP, Sabatini DM, Kaplin AI, Walensky LD, Snyder SH. Immunophilin FK506 binding protein associated with inositol-1,4,5-triphosphate receptors modulates calcium flux. Proc Natl Acad Sci USA 1995;92:1784-8.
11. Fruman DA, Klee CB, Bierer BE, Burakoff SJ. Calcineurin phosphatase activity in T-lymphocytes is inhibited by FK-506 and cyclosporine A. Proc Natl Acad Sci USA 1992;89:3686-90.
12. Lane BC, Miller LN, Kawai M, et al. Evaluation of calcineurin's role in the immunosuppressant activity of FK-506, related macrolactams, and cyclosporine. Transplant Proc 1993;25(1 pt 1):644-6.
13. Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL. Calcineurin is a common target of cyclophilin-cyclosporine and FKBP-FK-506 complexes. Cell 1991 ;66: 807-15.
14. Liu J, Albers MW, Wandless TJ, et al. Inhibition of T-cell signalling by immunophilin-ligand complexes correlates with loss of Calcineurin phosphatase activity. Biochemistry 1992;31:3896-3901.
15. Schreiber SL, Crabtree GR. The mechanism of action of cyclosporine A and FK-506. Immunol Today 1992;13:136-42.
16. Wiederrecht G, Lam E, Hung S, Martin M, Sigal N. The mechanism of action of FK-506 and cyclosporine A. Ann NY Acad Sci 1993;696:9-19.
17. Griffith JP, Kim JL, Kim EE, et al. X-ray structure of Calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell 1995;82:507-22.
18. Tocci MJ, Matkovich DA, Collier KA, et al. The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes. J Immunol 1989;143:718-26.
19. Dumont FJ, Melino MR, Staruch MJ, Koprak SL, Fischer PA, Sigal NH. The immunosuppressive macrolides FK-506 and rapamycin act as reciprocal antagonists in murine T cells. J Immunol 1990;144:1418-24.
20. Bierer BE, Mattila PS, Standaert RF, et al. Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin. Proc Natl Acad Sci USA 1990;87:9231-5.
21. Dumont FJ, Staruch MJ, Koprak SL, Melino MR, Sigal NH. Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. J lmmunol 1990;144:251-8.
22. Chen Y, Chen H, Rhoad A, et al. A putative sirolimus (rapamycin) effector protein. Biochem Biophys Res Commun 1994;203:1-7.
23. Price DJ, Grove JR, Calvo V, Avruch J, Bierer BE. Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase. Science 1992;257(5072):973-6.
24. Kuo CJ, Chung J, Fiorentino DF, Flanagan WM, Blenis J, Crabtree GR. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 1992;358(6381):70-3.
25. Chung J, Kuo CJ, Crabtree GR, Blenis J. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 1992;69:1227-36.
26. Calvo V, Crews CM, Vik TA, Bierer BE. lnterleukin-2 stimulation of p70 S6 kinase activity is inhibited by the immunosuppressant rapamycin. Proc Natl Acad Sci USA 1992;89:7571-5.
27. Erikson RL. Structure, expression, and regulation of the protein kinases involved in the phosphorylation of ribosomal protein S6. J Biol Chem 1991;266:6007-101.
28. Kozma SC, Thomas G. p70S6k/p85S6k: mechanism of activation and role in mitogenesis. Semin Cancer Biol 1994;5:255-60.
29. Brown EJ, Beal PA, Keith CT, et al. Control of p70S6 kinase by kinase activity of FRAP in vivo. Nature 1995;377(6548): 441-6.
30. Terada N, Patel HR, Takase K, Kohno K, Nairn AC, Gelfand EW. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc Natl Acad Sci USA 1994;91:11477-81.
31. Sherr CJ. G1 phase progression: cycling on cue. Cell 1994;79:551-5.
32. Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM, Pagano M. Human cyclin E, a nuclear protein essential for the G1-to-S-phase transition. Mol Cell Biol 1995;15:2612-24.
33. Nourse J, Firpo E, Flanagan WM, et al. Interleukin-2-mediated elimination of the p27kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 1994;372(6506):570-3.
34. Morice WG, Wiederrecht G, Brunn GJ, Siekierka JJ, Abraham RT. Rapamycin inhibition of interleukin-2-dependent p33ccdk2 and p34cdc2 kinase activation in T lymphocytes. J Biol Chem 1993;268:22737-45.
35. Morice WG, Brunn GJ, Wiederrecht G, Siekierka JJ, Abraham RT. Rapamycin-induced inhibition of p34cdc2 kinase activation is associated with G1/S-phase growth arrest in T-lymphocytes. J Biol Chem 1993;268:3734-8.
36. Schmandt R, Hill M, Amendola A, Mills GB, Hogg D. IL-2 induced expression of TTK, a serine, threonine, tyrosine kinase, correlates with cell cycle progression. J lmmunol 1994;152:96-105.
37. Jayaraman T, Marks AR. Rapamycin-FKBP12 blocks proliferation, induces differentiation, and inhibits cdc2 kinase activity in a myogenic cell line. J Biol Chem 1993;268:25385-8.
38. Flanagan WM, Crabtree GR. Rapamycin inhibits p34cdc2 expression and arrests T lymphocyte proliferation at the G1/S transition. Ann NY Acad Sci 1993;696:31-7.
39. Yatscoff RW. Pharmacokinetics of rapamycin. Transplant Proc 1996;28:970-3.
40. Yatscoff RW, Wang P, Chan K, Hicks D, Zimmerman J. Rapamycin: distribution, pharmacokinetics, and therapeutic range investigations. Ther Drug Monit 1995;17:666-71.
41. Johnson EM, Zimmerman J, Duderstadt K, et al. A randomized, double-blind, placebo-controlled study of the safety, tolerance, and preliminary pharmacokinetics of ascending single doses of orally administered sirolimus (rapamycin) in stable renal transplant recipients. Transplant Proc 1996;28:987.
42. Ferron GM, Mishina EV, Zimmerman JJ, Jusko WJ. Population pharmacokinetics of sirolimus in kidney transplant patients. Clin Pharmacol Ther 1997;61:416-28.
43. Zimmerman JJ, Kahan BD. Pharmacokinetics of sirolimus in stable renal transplant patients after multiple oral dose administration. J Clin Pharmacol 1997;37:405-15.
44. Brattstrom C, Tyden G, Sawe J, Herlenius G, Claesson K, Groth CG. A randomized, double-blind, placebo-controlled study of the safety, tolerance, and preliminary pharmacokinetics of ascending single doses of orally administered sirolimus (rapamycin) in stable renal transplant recipients. Transplant Proc 1996;28:985-6.
45. Kahan BD, Murgia MG, Slayton J, Napoli K. Potential applications of therapeutic drug monitoring of sirolimus immunosuppression in clinical renal transplantation. Ther Drug Monit 1995;17:672-5.
46. Napoli KL, Wang M, Stepkowski SM, Kahan BD. Distribution of sirolimus in rat tissue. Clin Biochem 1997;30:135-42.
47. Kay JE, Sampare-Kwateng E, Geraghty F, Morgan GY. Uptake of FK506 by lymphocytes and erythrocytes. Transplant Proc 1991;23:2760-2.
48. Yatscoff RW, LeGatt D, Keenan R, Chackowsky P. Blood distribution of rapamycin. Transplantation 1993;56:1202-6.
49. de Groen PC, Wiesner RH, Krom RA. Cyclosporin A induced side effects related to a low serum cholesterol level: an indication for a free cyclosporin A assay. Transplant Proc 1988; 20(2 suppl 2):374-6.
50. Verrill HL, Girgis RE, Easterling RE, Malhi BS, Mueller WF. Distribution of cyclosporine in blood of renal transplant recipient with type V hyperlipoproteinemia. Clin Chem 1987;33:423-8.
51. Sattler M, Guengerich FP, Yun CH, Christians U, Sewing KF. Cytochrome P-450 enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos 1992;20:753-61.
52. Christians U, Sattler M, Schiebel HM, et al. Isolation of two immunosuppressive metabolites after in vitro metabolism of rapamycin. Drug Metab Dispos 1992;20:186-91.
53. Calne RY,Collier D, Lim S, et al. Rapamycin for immunosuppression in organ allografting [letter]. Lancet 1989; 2(8656):227.
54. Morris RE, Meiser BM. Identification of a new pharmacologic action for an old compound [letter]. Med Sci Lett 1989;17:609-10.
55. Stepkowski SM, Chen H, Daloze P, Kahan BD. Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and small bowel transplantation in the rat. Transplantation 1991;51:22-6.
56. Collier D, Calne R, Thiru S, et al. Rapamycin in experimental renal allografts in dogs and pigs. Transplant Proc 1990;22: 1674-5.
57. Collier D, Calne RY, Pollard SG, Friend PJ, Thiru S. Rapamycin in experimental allografts in primates. Transplant Proc 1991;23:2246-7.
58. Gregory CR, Huie P, Billingham ME, Morris RE. Rapamycin inhibits arterial intimai thickening caused by both alloimmune and mechanical injury. Transplantation 1993;55:1409-18.
59. Gregory CR, Huang X, Pratt RE, et al. Treatment with rapamycin and mycophenolic acid reduces arterial intimal thickening produced by mechanical injury and allows endothelial replacement. Transplantation 1995;59:655-61.
60. Cao W, Mohacsi P, Shorthouse R, Pratt R, Morris RE. Effects of rapamycin on growth factor-stimulated vascular smooth muscle cell DNA synthesis. Transplantation 1995;59:390-5.
61. Kahan BD, Gibbons S, Tejpal N, Stepkowski SM, Chou TC. Synergistic interactions of cyclosporine and rapamycin to inhibit immune performances of normal human peripheral blood lymphocytes in vitro. Transplantation 1991;51:232-9.
62. Knight R, Ferraresso M, Serino F, Katz S, Lewis R, Kahan BD. Low-dose rapamycin potentiates the effects of subtherapeutic doses of cyclosporine to prolong renal allograft survival in the mongrel canine model. Transplantation 1993;55:947-9.
63. Murgia MG, Jordan S, Kahan BD. The side effect profile of sirolimus: a phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients. Kidney Int 1996;49:209-16.
64. Lindholm A, Kahan BD. Influence of cyclosporine pharmacokinetics, trough concentrations, and AUC monitoring on outcome after kidney transplantation. Clin Pharmacol Ther 1993;54:205-18.
65. Kahan BD, Katz SM, Jordan SM, Van Buren CT. Sirolimus permits rapid corticosteroid withdrawal from a cyclosporine-based regimen in renal transplantation [abstr]. Presented at 16th International Congress of the Transplantation Society, Barcelona, August 26, 1996.
66. Kahan BD, Pescovitz M, Julian B, Chan G, Vanrenterghem Y. Sirolimus multi-center study group. Multi-center phase II trial of Sirolimus (SRL) in renal transplantation: six-month results [abstr]. Presented at 16th International Congress of the Transplantation Society, Barcelona, August 26, 1996.
67. Neylan JF, Pescovitz MD, Julian BA, Chan G, Vanrenterghem Y, Kahan BD. Multi-center phase II trial of Sirolimus in renal transplantation: immunosuppressive requirements for black patients [abstr]. Presented at 16th International Congress of the Transplantation Society, Barcelona, August 26, 1996.
68. Fryer J, Yatscoff RW, Pascoe EA, Thliveris J. Relationship of blood concentrations of rapamycin and cyclosporine to suppression of allograft rejection in a rabbit heterotopic heart transplant model. Transplantation 1993;55:340-5.
69. Yakimets WJ, Lakey JR, Yatscoff RW, et al. Prolongation of canine pancreatic islet allograft survival with combined rapamycin and cyclosporine therapy at low doses: rapamycin efficacy is blood level related. Transplantation 1993;56:1293-8.
70. Granger DK, Cromwell JW, Chen SC, et al. Prolongation of renal allograft survival in a large animal model by oral rapamycin monotherapy. Transplantation 1995;59:183-6.
71. Yatscoff RW, Faraci C, Bolingbroke P. Measurement of rapamycin in whole blood using reverse-phase high performance liquid chromatography. Ther Drug Monit 1992;14:138-41.
72. Yatscoff RW, Boeckx R, Holt DW, et al. Consensus guidelines for therapeutic drug monitoring of rapamycin: report of the consensus panel. Ther Drug Monit 1995;17:676-80.
73. Napoli KL, Kahan BD. Sample clean-up and high performance liquid chromatography techniques for measurement of whole blood rapamycin concentrations. J Chromatogr Biomed Appl 1994;654:111-20.
74. Whiting PH, Woo J, Adam BJ, Hasan NU, Davidson RJL, Thomson AW. Toxicity of rapamycin - a comparative and combination study with cyclosporine at immunotherapeutic dosage in the rat. Transplantation 1991;52:203-8.