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Sirolimus: a comprehensive review
1Division of Immunology and Organ Transplantation, University of Texas-Houston, 6431 Fannin, Suite 6.240, Houston, TX 77030, USA. barry.d.kahan@uth.tmc.edu
Expert Opinion on Pharmacotherapy
|February 5, 2002
Summary
Sirolimus, an mTOR inhibitor, shows synergistic effects with cyclosporin A, significantly reducing acute rejection in renal transplants. This potent immunosuppressant may also mitigate chronic rejection by inhibiting vascular smooth muscle cell proliferation.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Sirolimus is a potent immunosuppressant for renal transplantation.
- It targets the mammalian target of rapamycin (mTOR) pathway.
- Sirolimus exhibits synergistic effects with cyclosporin A (CsA).
Purpose of the Study:
- To evaluate the efficacy and safety of sirolimus in renal transplantation.
- To assess the synergistic interaction between sirolimus and CsA.
- To explore sirolimus's potential in preventing chronic rejection.
Main Methods:
- Pivotal multi-center, blinded, dose-controlled trials.
- Tightly controlled concentrations of CsA and sirolimus.
- Administration of 2 or 5 mg/day sirolimus in combination with CsA and steroids.
Main Results:
- Acute rejection rates < 10% with controlled CsA and sirolimus concentrations.
- Reduced acute rejection rates of 19% and 14% with 2 and 5 mg/day sirolimus, respectively.
- Sirolimus inhibits cytokine-driven pathways and may retard endothelial and vascular smooth muscle cell proliferation.
Conclusions:
- Sirolimus is a potent immunosuppressant with synergistic effects with CsA in renal transplantation.
- It offers a unique mechanism of action potentially reducing chronic rejection.
- Myelosuppression and hyperlipidemia are noted side effects; ongoing studies assess long-term benefits regarding chronic nephropathy.