Test Summary
Sirolimus (Rapamycin)
Test code: 36712
Clinical use
- Monitor immunosuppressive therapy following organ transplant
Clinical background
Sirolimus (rapamycin, Rapamune®) is an immunosuppressant that inhibits cytokine-stimulated T-cell proliferation. Sirolimus acts by forming a complex with FK-binding protein-12 which in turn binds to mTOR kinase, a specific cell cycle regulatory protein, thereby inhibiting mTOR action.1 mTOR inhibition prevents cell cycle progression from G1 to S phase in T-cells and, thus, T-cell proliferation. mTOR inhibition is a different mechanism of action than that of calcineurin-inhibiting agents such as cyclosporine (CsA), a fact that may account for the synergistic effect of sirolimus/CsA combined therapy following renal transplant. Sirolimus is currently recommended for use in conjunction with CsA (and corticosteroids) to reduce or prevent graft rejection by the host.2 Sirolimus dose-related side effects include increased serum levels of cholesterol, triglycerides, and creatinine and decreased glomerular filtration rate. Hypertension, peripheral edema, anemia, arthralgia, diarrhea or constipation, thrombocytopenia, lymphoma, and skin cancer also may occur.
Sirolimus bioavailability and clearance are dependent on intestinal and hepatic metabolism by cytochrome P450 3A4 enzyme and on countertransport by the multidrug efflux pump p-glycoprotein in the intestine. Thus, coadministration of CYP450 3A4 and p-glycoprotein strong inducers and inhibitors should be avoided as they will either decrease or increase sirolimus bioavailability, respectively.2
Pharmacokinetics are also altered during drug coadministration. For example, when sirolimus is administered concomitantly with the microemulsion formulation of CsA rather than administered separately 4 hours apart, sirolimus trough levels increase.1 Pharmacokinetic studies reveal an approximate 4.5-fold range in interindividual behavior3 and a correlation between trough blood concentrations and both efficacy and toxicity.3,4
Individuals suitable for testing
All patients who have had an organ transplant and are receiving sirolimus therapy, especially those2
- Likely to have altered drug metabolism
- Weighing <88 pounds
- Who have switched from oral to tablet form or vice versa
- With hepatic impairment
- Who are receiving concurrent doses of strong CYP3A and p-glycoprotein inhibitors or inducers
Method
- Liquid chromatography/tandem mass spectrometry (LC/MS/MS)
- Limit of quantitation: 2.5 μg/L
- Specificity: no known interference
- Synonyms: rapamycin, Rapamune®
Interpretive information
Steady state trough sirolimus levels <3.0 μg/L may place the patient at risk for infection and host-graft rejection. Conversely, levels >18.0 μg/L are more likely to be associated with adverse events. As mentioned above, levels may be affected by drug coadministration and pharmacokinetics. Steady state is usually reached 5 to 7 days after a dose adjustment. Evaluation of multiple trough levels 7 days after the last dose change is recommended prior to a subsequent dose change.
Table. Interindividual Pharmacokinetic Variability
Oral solution2,5 |
Tablet2 |
|
Time to peak concentration (tmax) |
2.1±0.8 h |
3.5±2.4 h |
Terminal half-life (t½) |
62.3±16.2 h |
Not established |
Oral clearance rate (Cl/F) |
173±50 mL/h/kg |
139±63 mL/h/kg |
Apparent oral steady-state volume (Vss/F) |
12.0±4.6 L/kg |
Not established |
References
- MacDonald A, Scarola J, Burke JT, et al. Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus. Clin Ther. 2000;22(suppl 2):B101-B121. doi:10.1016/S0149-2918(00)89027-X
- Rapamune® (Sirolimus) Oral Solution and Tablets. Package insert. Wyeth Laboratories; 2018.
- Aspeslet LJ, Yatscoff RW. Requirements for therapeutic Drug monitoring of sirolimus, an immunosuppressive agent used in renal transplantation. Clin Ther. 2000;22(suppl 2):B86-B92. doi:10.1016/S0149-2918(00)89025-6
- Kahan BD, Napoli KL, Kelly PA, et al. Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity. Clin Transplant. 2000;14(2):97-109. doi:10.1034/j.1399-0012.2000.140201.x
- Zimmerman JJ, Kahan BD. Pharmacokinetics of sirolimus in stable renal transplant patients after multiple oral dose administration. J Clin Pharmacol. 1997;37(5):405-415. doi:10.1002/j.1552-4604.1997.tb04318.x
Content reviewed 06/2025
36712 - Sirolimus, LC/MS/MS
Drug Half-Life, Steady State, and Recommended Sample Collection Time
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
The tests listed by specialty and category are a select group of tests offered. For a complete list of Quest Diagnostics tests, please adjust the filter options chosen, or refer to our Directory of Services.