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Paediatric Laboratory Medicine

Sirolimus (Rapamycin)

Clinical Significance

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 affect 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 G 1 to the S phase of the cell cycle.

Studies in experimental models show that sirolimus prolongs allograft (kidney, heart, skin, islet, small bowel, pancreatico-duodenal, and bone marrow) survival. Sirolimus reverses acute rejection of heart and kidney allografts and prolongeds the graft survival. In some studies, the immunosuppressive effect of sirolimus lasted up to six months after discontinuation of therapy. This tolerization effect is alloantigen specific.

Test Name

Sirolimus (Rapamycin)

Alternate Name/ Synonym

Rapamycin

Test Code

SIROL

Division

Therapeutic Drug Monitoring - TDM

Method

LC-MS/MS

External Proficiency Testing

CAP
IPTS

Turn Around Time

Daily @ 10:30h

Disease/Condition

Immunosuppressive

Specimen Type

Whole Blood (EDTA) - Do not Separate

Minimum Specimen Requirements

200 uL

Optimal Collection Time

Trough: 0-30 minutes prior to dose

Storage/Transportation

4°C (transport with a cool pack if possible)

Approval is not required

CPT Codes

80195

Shipping and Contact Information

The Hospital for Sick Children
Rapid Response Laboratory
170 Elizabeth Street, Room 3642
Toronto, ON
M5G 2G3
Canada
Phone: 416-813-7200
Phone: 1-855-381-3212

Therapeutic Range

5.0–15.0 ug/L