Skip to main content
SpringerLink
Log in
Book cover

Modern Immunosuppressives pp 43–75Cite as

Birkhäuser

The potential role of immunosuppressive macrocyclic lactones

  • Chapter

  • 100 Accesses

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

Macrocyclic lactones are lipophilic molecules bearing a large 12-, 14-, or 16- membered lactone ring substituted with hydroxyl, methyl, and ethyl groups, as well as carbonyl functions with one, two, or three carbohydrate fragments. The first compound of this class, pikromycin, was isolated by Brockman et al. in 1950 [1]. The past three decades have witnessed the development and extensive use of a group of medium-to-narrow-spectrum antibiotic macrocyclic lac-tones: erythromycin, oleandomycin, leucomycin (kitasamycin), josamycin (leucomycin A3), acetylspiramycin, and midemycin.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brockman H, Henkel W (1950) Pikromycin, ein neues Antibiotikum aus Actinomycentin. Naturwissenschaften 37: 138

    Google Scholar 

  2. Eichenwald HF (1986) Adverse reactions to erythromycin. Pediatr Infect Dis 5: 147–150

    PubMed  CAS  Google Scholar 

  3. Hodak SP, Moubarak JB, Rodriguez I, Gelfand MC, Alijani MR, Tracy CM (1998) QT prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report. Transplantation 66: 535–537

    PubMed  CAS  Google Scholar 

  4. Johnson MC, So S, Marsh JW, Murphy AM (1992) QT prolongation and Torsades de Pointes after administration of FK506. Transplantation 53: 929–930

    PubMed  CAS  Google Scholar 

  5. Drici MD, Knollmann BC, Wang WX, Woosley RL (1998) Cardiac actions of erythromyc In: influence of female sex. JAMA 280: 1774–1776

    PubMed  CAS  Google Scholar 

  6. Antzelevitch C, Sun ZQ, Zhang ZQ, Yan GX (1996) Cellular and ionic mechanisms underlying erythromycin-induced long QT intervals and torsade de pointes. J Amer Coll Cardiol 28: 1836–1848

    CAS  Google Scholar 

  7. Guelon D, Bedock B, Chartier C, Haberer JP (1986) QT prolongation and recurrent “torsades de pointes” during erythromycin lactobionate infusion. Amer J Cardiol 58: 666

    PubMed  CAS  Google Scholar 

  8. Dumont FJ, Koprak S, Staruch MJ, Talento A, Koo G, DaSilva C, Sinclair PJ, Wong F, Woods J, Barker J et al (1998) A tacrolimus-related immunosuppressant with reduced toxicity. Transplantation 65: 18–26

    PubMed  CAS  Google Scholar 

  9. Peterson LB, Cryan JG, Rosa R, Martin MM, Wilusz MB, Sinclair PJ, Wong F, Parsons JN, O’Keefe SJ, Parsons WH et al (1998) A tacrolimus-related immunosuppressant with biochemical properties distinct from those of tacrolimus. Transplantation 65: 10–18

    PubMed  CAS  Google Scholar 

  10. Goto T, Kino T, Hatanaka H, Nishiyama M, Okuhara M, Kohsaka M, Aoki H, Imanaka H (1987) Discovery of FK506, a novel immunosupressant isolated from Streptomyces tsukubaensis. Transplant Proc 19 (5 Suppl 6): 4–8

    PubMed  CAS  Google Scholar 

  11. Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A (1989) FK506 for liver, kidney, and pancreas transplantation. Lancet 2: 1000–1004

    PubMed  CAS  Google Scholar 

  12. Johansson A, Moller E (1990) Evidence that the immunosuppress ve effects of FK506 and cyclosporine are identical. Transplantation 50: 1001–1007

    PubMed  CAS  Google Scholar 

  13. Henderson DJ, Naya I, Bundick RV, Smith GM, Schmidt JA (1991) Comparison of the effects of FK506, cyclosporine A, and rapamycin on IL-2 production. Immunology 73: 316–321

    PubMed  CAS  Google Scholar 

  14. Hutchinson IV (1997) The mode of action of Prograf (tacrolimus) and its significance for longterm graft survival. New Horizons in Kidney Transplantation 1: 22

    Google Scholar 

  15. Migita K, Eguchi K, Kawabe T, Tsukada T, Mizokami A, Nagasaki S (1995) FK506 augments activation-induced programmed cell death of T lymphocytes in vivo. J Clin Invest 96: 727–732

    PubMed  CAS  Google Scholar 

  16. Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, McMichael J, Lever J, Burckart G, Starzl T (1995) Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet 29: 404–430

    PubMed  CAS  Google Scholar 

  17. Ihara H, Shinkuma D, Ichikawa Y, Nojima M, Nagano S, Ikoma F (1995) Intra-and interindividual variation in the pharmacokinetics of tacrolimus (FK506) in kidney transplant recipients - importance of trough level as a practical indicator. Int J Urol 2: 151–155

    PubMed  CAS  Google Scholar 

  18. Laskow DA, Vincenti F, Neylan JF, Mendez R, Matas AJ (1996) An open-label, concentration-ranging trial of FK506 in primary kidney transplantation. Transplantation 62: 900–905

    PubMed  CAS  Google Scholar 

  19. Jain AB, Abu-Elmagd K, Abdallah H, Warty V, Fung J, Todo S, Starzl TE, Venkataramanan R (1993) Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion. J Clin Pharmacol 33: 606–611

    PubMed  CAS  Google Scholar 

  20. Jain AB, Venkataramanan R, Cadoff E, Fung JJ, Todo S, Krajack A, Starzl TE (1990) Effect of hepatic dysfunction and T-tube clamping on FK506 pharmacokinetics and trough concentrations. Transplant Proc 22: 57–59

    PubMed  CAS  Google Scholar 

  21. Jusko WJ, Thomson AW, Fung J, McMaster P, Wong SH, Zylber-Katz E, Christians U, Winkler M, Fitzsimmons WE, Lieberman R et al (1995) Consensus document: therapeutic monitoring of tacrolimus (FK506). Ther Drug Monit 17: 606–614

    PubMed  CAS  Google Scholar 

  22. Jusko WJ (1995) Analysis of tacrolimus (FK506) in relation to therapeutic drug monitoring. Ther Drug Monit 17: 596–601

    PubMed  CAS  Google Scholar 

  23. Vathsala A, Goto S, Yoshimura N, Stepkowski S, Chou TC, Kahan BD (1991) The immunosuppressive antagonism of low doses of FK506 and cyclosporine. Transplantation 52: 121–128

    PubMed  CAS  Google Scholar 

  24. Zhang Q, Simpson J, Aboleneen HI (1997) A specific method for the measurement of tacrolimus on human whole blood by liquid chromatography/tandem mass spectrometry. Ther Drug Monit 19: 470–476

    PubMed  CAS  Google Scholar 

  25. Alak AM (1997) Measurement of tacrolimus (FK506) and its metabolites: a review of assay development and application in therapeutic drug monitoring and pharmacokinetic studies. Ther Drug Monit 19: 338–351

    PubMed  CAS  Google Scholar 

  26. Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS (1997) A comparison of tacrolimus and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 63: 977–983

    PubMed  CAS  Google Scholar 

  27. Neylan JF (1998) Racial differences in renal transplantation after immunosuppression with tacrolimus versus cyclosporine. FK506 Kidney Transplant Study Group. Transplantation 65: 515–523

    PubMed  CAS  Google Scholar 

  28. Heifets M, Cooney G, Shaw L (1996) Ethnic differences in tacrolimus pharmacokinetics in renal transplant candidates. Annual Meeting of the American Society of Transplant Physicians

    Google Scholar 

  29. Andrews PA, Sen M, Chang RW (1996) Racial variation in dosage requirements of tacrolimus. Lancet 348: 1446

    PubMed  CAS  Google Scholar 

  30. Katari SR, Magnone M, Shapiro R, Jordan M, Scantlebury V, Vivas C, Gritsch A, McCauley J, Starzl T, Demetris AJ et al (1997) Clinical features of acute reversible tacrolimus (FK506) nephrotoxicity in kidney transplant recipients. Clin Transplant 11: 237–242

    PubMed  CAS  Google Scholar 

  31. Randhawa PS, Shapiro R, Jordan ML, Starzl TE, Demetris AJ (1993) The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506. Amer J Surg Pathol 17: 60–68

    CAS  Google Scholar 

  32. Radermacher J, Meiners M, Bramlage C, Kliem V, Behrend M, Schlitt HJ, Pichlmayr R, Koch KM, Brunkhorst R (1998) Pronounced renal vasoconstriction and systemic in renal transplant patients treated with cyclosporine A versus FK 506. Transplant Int 11: 3–10

    CAS  Google Scholar 

  33. Shapiro R, Jordan ML, Scantlebury VP, Vivas C, McCauley J, Johnston J, Fung JJ, Starzl TE (1998) Alopecia as a consequence of tacrolimus therapy. Transplantation 65: 1284

    PubMed  CAS  Google Scholar 

  34. Wiesner RH (1998) A long term comparison of tacrolimus (FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 study group. Transplantation 66: 493–499

    PubMed  CAS  Google Scholar 

  35. Anonymous (1994) A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation. The U.S. Multicenter FK506 Liver Study Group. N Engl J Med 331: 1110–1115

    Google Scholar 

  36. Fung J, Eliaziw M, Todo S, Jain A, Demetris AJ, McMichael JP, Starzl TE, Meier P, Donner A (1996) The Pittsburgh randomized trial of tacrolimus compared to cyclosporine for hepatic transplantation. J Amer Coll Surg 183: 117–125

    CAS  Google Scholar 

  37. Williams R, Neuhaus P, Bismuth H, McMaster P, Pichlmayr R, Caine R, Otto G, Groth C (1996) Two-year data from the European multicentre tacrolimus (FK506) liver study. Transplant Int 9 Suppl 1: S144–S150

    Google Scholar 

  38. Jonas S, Kling N, Bechstein WO, Blumhardt G, Lohmann R, Lobeck H, Neuhaus P (1995) Rejection episodes after liver transplantation during primary immunosuppression with FK506 or a cyclosporine-based regimen: a controlled, prospective, randomized trial. Clin Transplant 9: 406–414

    PubMed  CAS  Google Scholar 

  39. Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M et al (1997) Multicenter randomized trial comparing tacrolimus and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 64: 436–443

    PubMed  CAS  Google Scholar 

  40. Gruessner A, Sutherland DE (1994) Pancreas transplant results in the United Network for Organ Sharing (UNOS) United States of America (USA) Registry compared with non-USA data in the International Registry. Clin Transplant 47–68

    Google Scholar 

  41. Shaffer D, Simpson MA, Conway P, Madras PN, Monaco AP (1995) Normal pancreas allograft function simultaneous pancreas kidney transplantation after rescue therapy with tacrolimus (FK506). Transplantation 59: 1063–1066

    PubMed  CAS  Google Scholar 

  42. Hariharan S, Peddi VR, Munda R, Demmy AM, Schroeder TJ, Alexander JW, First MR (1997) Long-term renal and pancreas function with tacrolimus rescue therapy following pancreas transplantation. Transplant Proc 29: 652–653

    PubMed  CAS  Google Scholar 

  43. Hariharan S, Munda R, Demmy TJ, Shroeder TJ, Alexander JW, First MR (1995) Conversion from cyclosporine to tacrolimus after pancreas transplantation. Transplant Proc 27: 2981–2982

    PubMed  CAS  Google Scholar 

  44. Teroaka S, Babazono T, Koike T, Abe M, Kimikawa M, Shinkai M, Haruguchi H, Hirotani S, Kitajima K, Akamatsu M et al (1995) Effect of rescue therapy using FK506 on relapsing rejection after combined pancreas and kidney transplantation. Transplant Proc 27: 1335–1339

    Google Scholar 

  45. Gruessner RW, Burke GW, Stratta R, Sollinger H, Benedetti E, Marsh C, Stock P, Boudreaux JP, Martin M, Drangstveit MB et al (1996) A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation. Transplantation 61: 261–273

    PubMed  CAS  Google Scholar 

  46. Pham SM, Kormos RL, Hattler BG, Kawai A, Tsamandas AC, Demetris AJ, Murali S, Fricker FJ, Chang HC, Jain AB et al (1996) A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results. J Thorac Cardiovasc Surg 111: 764–772

    PubMed  CAS  Google Scholar 

  47. Reichart B, Meiser B, Vigano M, Rinaldi M, Martinelli L, Yacoub M, Banner NR, Gandjbakhch I, Dorent R, Hetzer R et al (1998) European Multicenter Tacrolimus (FK506) heart pilot study: one-year results - European Tacrolimus Multicenter Heart Study Group. J Heart Lung Transplant 17: 775–781

    PubMed  CAS  Google Scholar 

  48. Tsamandas AC, Pham SM, Seaberg EC, Pappo O, Kormos RL, Kawai A, Griffith BP, Zeevi A, Duquesnoy R, Fung B et al (1997) Adult heart transplantation under tacrolimus (FK506) immunosuppression: histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction. J Heart Lung Transplant 16: 723–734

    PubMed  CAS  Google Scholar 

  49. Keenan RJ, Konishi H, Kawai A, Paradis IL, Nunley DR, Iacono AT, Hardesty RL, Weyant RJ, Griffith BP (1995) Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg 60: 580–585

    PubMed  CAS  Google Scholar 

  50. Klintmalm GB, Goldstein R, Gonwa T, Wiesner RH, Krom RA, Shaw BW Jr, Stratta R, Ascher NL, Roberts JW, Lake J et al (1993) Use of Prograf (FK506) as rescue therapy for refractory rejection after liver transplantation. Transplant Proc 25 (1 Pt 1): 679–688

    PubMed  CAS  Google Scholar 

  51. Sher LS, Cosenza CA, Michel J, Makowka L, Miller CM, Schwartz ME, Busuttil R, McDiarmid S, Burdick JF, Klein AS et al (1997) Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group. Transplantation 64: 258–263

    PubMed  CAS  Google Scholar 

  52. Jain A, Fung J, Todo S (1996) More than six years actual follow-up: conversion from cyclosporine to tacrolimus for chronic liver allograft rejection. Hepatology 24: 181

    Google Scholar 

  53. Fung J, Todo S, Tsakis A, Demetris A, Jain A, Abu-Elmaged K, Alessiani M, Starzl TE (1991) Conversion of liver allograft recipients from cyclosporine to FK506-based immunosuppression: benefits and pitfalls. Transplant Proc 23: 14–21

    PubMed  CAS  Google Scholar 

  54. Jordan ML, Naraghi R, Shapiro R, Smith D, Vivas CA, Scantlebury VP, Gritsch HA, McCauley J, Randhawa P, Demetris AJ et al (1997) Tacrolimus rescue therapy for renal allograft rejection - five-year experience. Transplantation 63: 223–228

    PubMed  CAS  Google Scholar 

  55. Woodle ES, Thistlethwaite JR, Gordon JH, Laskow D, Deierhoi MH, Burdick J, Pirsch JD, Sollinger H, Vincenti F, Burrows L (1996) A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group. Transplantation 62: 594–599

    PubMed  CAS  Google Scholar 

  56. Mentzer RM Jr, Jahania MS, Lasley RD (1998) Tacrolimus as a rescue immunosuppressant after heart and lung transplantation. The U.S. Multicenter FK506 Study Group. Transplantation 65: 109–113

    PubMed  CAS  Google Scholar 

  57. Keown P, Niese D (1988) Cyclosporine microemulsion increases drug exposure and reduces acute rejection without incremental toxicity in de novo renal transplantation. International Sandimmun Neoral Study Group. Kidney Int 54: 938–944

    Google Scholar 

  58. Kahan BD (2000) Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group. Lancet 356: 194–202

    PubMed  CAS  Google Scholar 

  59. Vezina C, Kudelski A, Sehgal SN (1975) Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J Antibiot 28: 721–726

    PubMed  CAS  Google Scholar 

  60. Sehgal SN, Baker H, Vezina C (1975) Rapamycin (AY-22,989), a new antifungal antibiotic. II. Fermentation, isolation and characterization. J Antibiot 28: 727–732

    PubMed  CAS  Google Scholar 

  61. Eng CP, Sehgal SN, Vezina C (1984) Activity of rapamycin (AY-22,989) against transplanted tumors. J Antibiot 37: 1231–1237

    PubMed  CAS  Google Scholar 

  62. Kuo CJ, Chung J, Fiorentino DF, Flanagan WM, Blenis J, Crabtree GR (1992) Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 358: 70–73

    PubMed  CAS  Google Scholar 

  63. Stepkowski SM, Chen H, Daloze P, Kahan BD (1991) Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and small bowel transplantation in the rat. Transplantation 51: 22–26

    PubMed  CAS  Google Scholar 

  64. Kahan BD, Gibbons S, Tejpal N, Stepkowski SM, Chou TC (1991) Synergistic interactions of cyclosporine and rapamycin to inhibit immune performances of normal human peripheral blood lymphocytes in vitro. Transplantation 51: 232–239

    PubMed  CAS  Google Scholar 

  65. Brown EJ, Albers MW, Shin TB, Ichikawa K, Keith CT, Lane WS, Schreiber SL (1994) A mammalian protein targeted by Gl-arresting rapamycin-receptor complex. Nature 369: 756–758

    PubMed  CAS  Google Scholar 

  66. Brown EJ, Beal PA, Keith CT, Chen J, Shin TB, Schreiber SL (1995) Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature 377: 441–446

    PubMed  CAS  Google Scholar 

  67. Ferraresso M, Tian L, Ghobrial R, Stepkowski SM, Kahan BD (1994) Rapamycin inhibits production of cytotoxic but not noncytotoxic antibodies and preferentially activates Th2 cells that mediate long-term survival of heart allografts in rats. J Immunol 153: 3307–3318

    PubMed  CAS  Google Scholar 

  68. Napoli KL, Kahan BD (1996) Routine clinical monitoring of sirolimus (rapamycin) whole-blood concentrations by HPLC with ultraviolet detection. Clin Chem 42: 1943–1948

    PubMed  CAS  Google Scholar 

  69. Zimmerman JJ, Kahan BD (1997) Pharmacokinetics of sirolimus in stable renal transplant patients after multiple oral dose administration. J Clin Pharmacol 37: 405–415

    PubMed  CAS  Google Scholar 

  70. Yatscoff RW, Wang P, Chan K, Hicks D, Zimmerman J (1995) Rapamyc ln: distribution, pharmacokinetics, and therapeutic range investigations. Ther Drug Monit 17: 666–671

    PubMed  CAS  Google Scholar 

  71. Lown KS, Mayo RR, Leichtman AB, Hsiao HL, Turgeon DK, Schmiedlin-Ren P, Brown MB, Guo W, Rossi SJ, Benet LZ et al (1997) Role of intestinal P-glycoprotein (mdrl) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther 62: 248–260

    PubMed  CAS  Google Scholar 

  72. Wacher VJ, Wu CY, Benet LZ (1995) Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoproteln: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinogen 13: 129–134

    CAS  Google Scholar 

  73. Hebert MF, Roberts JP, Prueksaritanont Benet LZ (1992) Bioavailability of cyclosporine with concomittant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin Pharmacol Ther 54: 453–457

    Google Scholar 

  74. Kelly PA, Napoli KL, Dunne C, Kahan BD (1997) Conversion from liquid to solid sirolimus formulations in stable renal allograft transplant recipients. XVI Meeting of the American Society of Transplant Physicians Abstract A236

    Google Scholar 

  75. Murgia MG, Jordan S, Kahan BD (1996) The side-effect profile of sirolimus: A phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients. Kidney Int 49: 209–216

    PubMed  CAS  Google Scholar 

  76. Grevel J, Welsh MS, Kahan BD (1989) Cyclosporine monitoring in renal transplantation: area under the curve monitoring is superior to trough-level monitoring. Ther Drug Monit 11: 246–248

    PubMed  CAS  Google Scholar 

  77. Kahan BD, Welsh M, Rutzky LP (1995) Challenges in cyclosporine therapy: the role of therapeutic drug monitoring by area under the curve monitoring. Ther Drug Monit 17: 621–624

    PubMed  CAS  Google Scholar 

  78. Kaplan B, Meier-Kriesche H-U, Napoli K, Kahan BD (1997) A limited sampling strategy for estimating sirolimus area-under-the-concentration-curve. Clin Chem 43: 539–540

    PubMed  CAS  Google Scholar 

  79. Kahan BD (1998) The role of rapamycin in chronic rejection prophylaxis: a theoretical consideration. Graft 1 (2 Suppl II): 93

    Google Scholar 

  80. Kahan BD, Podbielski J, Napoli KL, Katz SM, Meier-Kriesche H-U, Van Buren CT (1998) Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation. Transplantation 66: 1040–1046

    PubMed  CAS  Google Scholar 

  81. Kahan BD, Julian BA, Pescovitz MD, Vanrenterghem Y, Neylan J (1999) Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. Transplantation 68: 1526–1532

    PubMed  CAS  Google Scholar 

  82. Dimeny E, Fellstrom B, Larsson E, Tufveson G, Lithell H (1993) Hyperlipoproteinemia in renal transplant recipients: is there a linkage with chronic vascular rejection? Transplant Proc 25: 2065–2066

    PubMed  CAS  Google Scholar 

  83. Dimeny E, Tufveson G, Lithell H, Larsson E, Siegbahn A, Fellstrom B (1993) The influence of pretransplant lipoprotein abnormalities on the early results of renal transplantation. Eur J Clin Invest 23: 572–579

    PubMed  CAS  Google Scholar 

  84. Groth CG, Backman L, Morales JM, Caine R, Kreis H, Lang P, Touraine JL, Claesson K, Campistol JM, Durand D et al (1999) Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation 67: 1036–1042

    PubMed  CAS  Google Scholar 

  85. MacDonald AS for the RAPAMUNEGlobal Study Group (1998) A randomized, placebo-controlled trial of rapamune in primary renal allograft recipients. Abstracts of the Transplantation Society XXVH World Congress Abstract 426

    Google Scholar 

  86. Slaton JW, Kahan BD (1996) Case report - sirolimus rescue therapy for refractory renal allograft rejection. Transplantation 61: 977–979

    PubMed  CAS  Google Scholar 

  87. Kahan BD, Podbielski J, Van Buren CT (1998) Rapamycin for refractory renal allograft rejection. XVII Annual Meeting of the American Society of Transplant Physicians Abstract 711

    Google Scholar 

  88. Pescovitz MD, Kahan BD, Julian B, Neylan J, Chan G (1997) Sirolimus (SRL) permits early steroid withdrawal from a triple therapy renal prophylaxis regimen. XVI Annual Meeting of the American Society for Transplant Physicians Abstract 708

    Google Scholar 

  89. Almond PS, Matas A, Gillingham K, Dunn DL, Payne WD, Gores P, Gruessner R, Najarian JS (1993) Risk factors for chronic rejection in renal allograft recipients. Transplantation 55: 752–756

    PubMed  CAS  Google Scholar 

  90. Kahan BD, Welsh M, Schoenberg L, Rutzky LP, Katz SM, Urbauer DL, Van Buren CT (1996) Variable oral absorption of cyclosporine. A biopharmaceutical risk factor for chronic renal allograft rejection. Transplantation 62: 599–606

    PubMed  CAS  Google Scholar 

  91. Marx SO, Jayaraman T, Go LO, Marks AR (1995) Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 76: 412–417

    PubMed  CAS  Google Scholar 

  92. Akselband Y, Harding MW, Nelson PA (1991) Rapamycin inhibits spontaneous and fibroblast growth factor beta-stimulated proliferation of endothelial cells and fibroblasts. Transplant Proc 23: 2833–2836

    PubMed  CAS  Google Scholar 

  93. Graves LM, Bornfeldt KE, Argast GM, Krebs EG, Kong X, Lin TA, Lawrence JC Jr, (1995) cAMP- and rapamycin-sensitive regulation of the association of eukaryotic initiation factor 4E and the translational regulator PHAS-I in aortic smooth muscle cells. Proc Natl Acad Sci USA 92: 7222–7226

    PubMed  CAS  Google Scholar 

  94. Mohacsi PJ, Tuller D, Hullinger B, Wijngaard PL (1997) Different inhibitory effects of immunosuppressive drugs on human and rat aortic smooth muscle and endothelial cell proliferation stimulated by platelet-derived growth factor or endothelial cell growth factor. J Heart Lung Transplant 16: 484–492

    PubMed  CAS  Google Scholar 

  95. Simm A, Nestler M, Hoppe V (1997) PDGF-AA, a potent mitogen for cardiac fibroblasts from adult rats. J Mol Cell Cardiol 29: 357–368

    PubMed  CAS  Google Scholar 

  96. Scott PH, Belham CM, al-Hafidh J, Chilvers ER, Peacock AJ, Gould GW, Plevin R (1966) A regulatory role for cAMP in phosphatidylinositol 3-kinase/p70 ribosomal S6 kinase-mediated DNA synthesis in platelet-derived-growth-factor-stimulated bovine airway smooth-muscle cells. Biochem J 318: 965–971

    Google Scholar 

  97. Obata T, Kashiwagi A, Maegawa H, Nishio Y, Ugi S, Hidaka H, Kikkawa R (1996) Insulin signaling and its regulation of system A amino acid uptake in cultured rat vascular smooth muscle cells. Circ Res 79: 1167–1176

    PubMed  CAS  Google Scholar 

  98. Gregory CR, Huang X, Pratt RE, Nishio Y, Ugi S, Hidaka H, Kikkawa R (1995) Treatment with rapamycin and mycophenolic acid reduces arterial intimal thickening produced by mechanical injury and allows endothelial replacement. Transplantation 59: 655–661

    PubMed  CAS  Google Scholar 

  99. Geerling RA, de Bruin RWF, Scheringa M, Bonthuis F, Jeekel J, Ijzermans JN, Marquet RL (1994) Suppression of acute rejection prevents graft arteriosclerosis after allogenic aorta transplantation in the rat. Transplantation 58: 1258–1263

    PubMed  CAS  Google Scholar 

  100. Calne RY, Collier DS, Lim S, Pollard SG, Samaan A, White DJ, Thiru S (1989) Rapamycin for immunosuppression in organ allografting. Lancet 2: 227

    PubMed  CAS  Google Scholar 

  101. Meiser BM, Billingham ME, Morris RE (1991) Effects of cyclosporin, FK506, and rapamycin on graft-vessel disease. Lancet 338: 1297–1298

    PubMed  CAS  Google Scholar 

  102. Morris RE, Huang X, Gregory CR, Billingham ME, Rowan R, Shorthouse R, Berry GJ (1995) Studies in experimental models of chronic rejection: use of rapamycin (sirolimus) and isoxazole derivatives (leflunomide and its analogue) for the suppression of graft vascular disease and obliterative bronchiolitis. Transplant Proc 27: 2068–2069

    PubMed  CAS  Google Scholar 

  103. Schmid C, Heemann U, Tilney NL (1997) Factors contributing to the development of chronic rejection in heterotopic rat heart transplantation. Transplantation 64: 222–228

    PubMed  CAS  Google Scholar 

  104. Kahan BD, Wong RL, Carter C, Katz SH, Von Fellenberg J, Van Buren CT, Appel-Dingemanse S (1999) A phase I study of a 4-week course of SDZ-RAD (RAD) quiescent cyclosporine-prednisone-treated renal transplant recipients. Transplantation 68: 1100–1106

    PubMed  CAS  Google Scholar 

  105. Dumont FJ, Melino MR, Staruch MJ, Koprak SL, Fisher PA, Sigal NH (1990) The immunosuppressive macrolides FK506 and rapamycin act as reciprocal antagonist in murine T-cells. J Immunol 144: 1418–1424

    PubMed  CAS  Google Scholar 

  106. Vu MD, Qi S, Xu D, Wu J, Fitzsimmons WE, Sehgal SN, Dumont L, Busque S, Daloze P, Chen H (1997) Tacrolimus (FK506) and sirolimus (rapamycin) in combination are not antagositic but produce extended graft survival in caridac transplantation in the rat. Transplantation 64: 1853–1856

    PubMed  CAS  Google Scholar 

  107. Chen H, Qi S, Xu D, Fitzsimmons WE, Bekersky I, Sehgal SN, Daloze P (1998) Combined effect of rapamycin and FK506 in prolongation of small bowel graft survival in the mouse. Transplant Proc 30: 2579–2581

    PubMed  CAS  Google Scholar 

  108. Vu MD, Qi S, Xu D, Wu J, Peng J, Daloze P, Sehgal S, Leduc B, Chen H (1998) Synergistic effects of mycophenolate mofetil and sirolimus in prevention of acute heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat. Transplantation 66: 1575–1580

    PubMed  CAS  Google Scholar 

  109. Hong JC, Kahan BD (1998) Two paradigms for new immunosuppressive strategies in organ transplantation. Curr Opin Organ Transplant 3: 175

    Google Scholar 

  110. Hong JC, Kahan BD (1999) Use of anti-CD25 monoclonal antibody in combination with rapamycin to eliminate cyclosporine treatment during the induction phase of immunosuppression. Transplantation 68: 701–704

    PubMed  CAS  Google Scholar 

  111. Wang ME, Stepkowski SM, Ferraresso M, Kahan BD (1992) Evidence that rapamycin rescue therapy delays rejection of major (MHC) plus minor (non-MHC) histoincompatible heart allografts in rats. Transplantation 54: 704–709

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Organ Transplantation, Department of Surgery, The University of Texas Medical School at Houston, 6431 Fannin Street, Suite 6.240, Houston, TX, 77030, USA

    Johnny C. Hong & Barry D. Kahan

Authors
  1. Johnny C. Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barry D. Kahan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Novartis Pharma AG, USA

    Henk-Jan Schuurman

  2. Novartis Pharma AG, Basel, 4002, Switzerland

    Gilles Feutren

  3. Immunologie Clinique, Hôpital Necker, 161 Rue de Sèvres, Paris Cedex 15, France

    Jean-François Bach

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Basel AG

About this chapter

Cite this chapter

Hong, J.C., Kahan, B.D. (2001). The potential role of immunosuppressive macrocyclic lactones. In: Schuurman, HJ., Feutren, G., Bach, JF. (eds) Modern Immunosuppressives. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8352-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8352-8_4

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9530-9

  • Online ISBN: 978-3-0348-8352-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation