Toxicity and efficacy of sirolimus: Relationship to whole-blood concentrations

Clinical Therapeutics

Volumn 22, Issue SUPPL. B, 2000, Pages

  Meier Kriesche, Herwig Ulf ^a   Kaplan, Bruce ^a,b  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

Author keywords

Concentrations; Efficacy; Pharmacokinetics; Sirolimus; Toxicity

Indexed keywords

AZATHIOPRINE; RAPAMYCIN;

ARTICLE; BLOOD TOXICITY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG METABOLISM; HUMAN; HYPERLIPIDEMIA; THROMBOCYTOPENIA;

EID: 0034070977     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/S0149-2918(00)89026-8     Document Type: Article

References (31)

1. 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.
2. MacDonald AS. A randomized trial of sirolimus, cyclosporine and prednisone vs cyclosporine-prednisone alone in recipients of mismatched first kidney grafts: Results at one year. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 1048.
3. Kahan BD. Pivotal phase II multi-center, randomized, blinded trial of sirolimus versus azathioprine in combination with cyclosporine and prednisone in primary renal transplants. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 68.
4. Kahan BD, Podbielski J, Napoli KL, et al. Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation. Transplantation. 1998;66:1040-1046.
5. Groth CG, Backman L, Morales JM, et al. Sirolimus (rapamycin)-based therapy in human renal transplantation: Similar efficacy and different toxicity compared with cyclosporine. Transplantation. 1999;67: 1036-1042.
6. Hong JC, Kahan BD. Use of anti-CD25 monoclonal antibody in combination with rapamycin to eliminate cyclosporine treatment during the induction phase of immunosuppression. Transplantation. 1999; 68:701-704.
7. Stepkowski SM, Napoli KL, Wang M, et al. Effects of the pharmacokinetic interaction between orally administered sirolimus and cyclosporine on the synergistic prolongation of heart allograft survival in rats. Transplantation. 1996;62:986-994.
8. Longoria J, Roberts RF, Marboe CC, et al. Sirolimus (rapamycin) potentiates cyclosporine in prevention of acute lung rejection. J Thorac Cardiovasc Surg. 1999;117:714-718.
9. Stepkowski SM, Tian L, Napoli KL, et al. Synergistic mechanisms by which sirolimus and cyclosporine inhibit rat heart and kidney allograft rejection. Cancer Chemother Pharmacol. 1996;33:325-330.
10. Ferron GM, Mishina EV, Zimmerman JJ, Jusko WJ. Population pharmacokinetics of sirolimus in kidney transplant patients. Clin Pharmacol Ther. 1997;61:416-428.
11. 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;28:987-993.
12. Yatscoff RW, Wang P, Chan K, et al. Rapamycin: Distribution, pharmacokinetics, and therapeutic range investigations. Ther Drug Monit. 1995;17:666-671.
13. Vu MD, Qi S, Xu D, et al. Synergistic effects of mycophenolate mofetil (MMF) and sirolimus (rapamycin, RAPA) in prevention of acute heart, pancreas and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 676.
14. Napoli KL, Wang M, Stepkowski SM, et al. Distribution of sirolimus in rat tissue. Clin Biochem. 1997;30:135-142.
15. Napoli KL, Wang ME, Stepkowski SM, Kahan BD. Relative tissue distributions of cyclosporine and sirolimus after concomitant peroral administration to the rat: Evidence for pharmacokinetic interactions. Ther Drug Monit. 1997;20:123-133.
16. Sattler M, Guengerich FP, Yun CH, et al. Cytochrome P-450 enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos. 1992;20:753-761.
17. Kahan BD, Napoli KL, Mosheim M, et al. Pharmacokinetic and pharmacodynamic correlation of cyclosporine (CSA) and rapamycin (RAPA) in 120 patients treated for at least 2 years at a single center. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 788.
18. Kaplan B, Meier-Kriesche H, Napoli K, et al. The effects of relative timing of sirolimus and cyclosporine microemulsion formulation coadministration on the pharmacokinetics of each agent. Clin Pharmacol Ther. 1998;63:48-53.
19. Zimmerman JJ, Kahan BD. Pharmacokinetics of sirolimus in stable renal transplant recipients after multiple oral dose administration. J Clin Pharmacol. 1997;37: 405-415.
20. Kahan BD. Pivotal phase III multicenter randomized, blinded trial of sirolimus versus azathioprine in combination with cyclosporine and prednisone in primary renal transplants. Transplantation. 1999; 67:68. Abstract.
21. Rakesh S, Wickersham PS, Jaffe JS, et al. Outcomes of African Americans (AA) in a phase III randomized placebo-controlled trial of sirolimus (SRL) in renal transplantation. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 925.
22. Neylan JF, Wickersham P, Jaffe J. Effect of race on efficacy and safety of sirolimus vs AZA plus standard immunotherapy in renal transplantation. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 924.
23. 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;56:1293-1298.
24. Fryer J, Yatscoff RW, Pascoe EA, et al. Relationship of blood concentrations of rapamycin and cyclosporine to suppression of allograft rejection in a rabbit heterotopic heart transplant model. Transplantation. 1993;55:340-345.
25. Kahan BD, Zimmerman J, Scarola J, et al. Kinetic-dynamic correlations of sirolimus and cyclosporine in 438 primary renal transplant recipients. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 23.
26. Kahan BD, Podbielski J, Napoli K, et al. Immunosuppressive effects and safety of a sirolimus/cyclosporine combination regimen for renal transplantation. Transplantation. 1998;66:1040-1046.
27. Kahan BD, Jaffe JS. Triglyceride (TG) elevations in renal transplant recipients treated with sirolimus (rapamycin, RAPA) added to a cyclosporine (CsA)/prednisone (Pred) regimen. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 172.
28. DiJoseph JF, Mihatsch MJ, Sihgal SN. Renal effect of rapamycin in the spontaneously hypertensive rat. Transplant Int. 1994;7:83-88.
29. Andoh TF, Burdmann EA, Franceschini N, et al. Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506. Kidney Int. 1996;50:1110-1117.
30. Andoh TF, Lindsley J, Franceschini N, Bennet WM. Synergistic effects of cyclosporine and rapamycin in a chronic nephrotoxicity model. Transplantation. 1996;62:311-316.
31. Podder H, Stepkowski SM, Napoli KL, Kahan BD. Sirolimus exacerbates CsA-induced nephrotoxicity by raising CsA blood trough levels, but does not impair renal function by a pharmacodynamic interaction. In: Program and abstracts of the American Society of Transplantation and American Society of Transplant Surgeons Annual Meetings; May 15-21, 1999; Chicago, Ill. Abstract 206.