• Metabolism: Half Life: 57-63 hours
• Uses/Sources: Used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. [Wikipedia]
• Health Effects: Increased susceptibility to infection, lymphoma, and malignancy; bronchial anastomotic dehiscence in lung transplant patients; decline in renal function in long-term combination of cyclosporine with Rapamune; proteinuria. (L1874)
• Symptoms: The most common ( ≥ 30%) adverse reactions observed with Rapamune in clinical studies are: peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, constipation, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia. (L1874)
• Treatment: General supportive measures should be followed in all cases of overdose. Based on the low aqueous solubility and high erythrocyte and plasma protein binding of sirolimus, it is anticipated that sirolimus is not dialyzable to any significant extent. (L1712)
• Route of Exposure: Oral

• Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
• Toxicity: LD50: >800 mg/kg (oral, rat) (L1874) LD50: >800 mg/kg (oral, mice) (L1874)

Sirolimus inhibits T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin IL-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the S phase of the cell cycle.