What is being tested?This test measures the amount of sirolimus in the blood. Sirolimus is a relatively new
immunosuppressive drug that is given orally to patients who have had an organ transplant. Sirolimus is a compound produced by the
bacteria Streptomyces hygroscopicus. It was originally discovered in a soil sample from Rapa Nui (Easter Island), about 2,000 miles east of Chile in the South Pacific. When ingested, sirolimus is absorbed from the gastrointestinal tract. Concentrations peak in the blood within a couple of hours and then gradually decline. Only a small percentage of the dose taken is bioavailable – present in a form that the body can use. Sirolimus has a
half-life of about 60 hours. It is metabolized by the liver into several
metabolites and is excreted from the body in the stool (more than 90%) and urine (less than 2%).
The U.S. Food and Drug Administration (FDA) has currently approved sirolimus for use in adults who have kidney transplants. It appears to be less toxic to the kidneys than other options and can be given in conjunction with the other immunosuppressive drugs cyclosporine and tacrolimus. The FDA does not recommend the use of sirolimus with liver or lung transplants because there is insufficient evidence of its safety and efficacy. There are also insufficient data regarding its use in children and the elderly, and there are cautions against its use in pregnant and breastfeeding women. Like other immunosuppressive agents, sirolimus may cause side effects and adverse reactions and is associated with an increased risk of infection and the development of lymphoma.
Normally, a person’s immune system recognizes a transplanted kidney as foreign and begins to attack it. Sirolimus limits this response and helps to prevent organ rejection by inhibiting T-lymphocyte activation and proliferation and antibody production. Sirolimus levels in the blood must be maintained within a narrow therapeutic range. If the concentration is too low, organ rejection may occur; if it is too high, then the patient may have symptoms associated with toxicity. Typically, sirolimus is given with cyclosporine and corticosteroids. Dosages must be tailored to the individual, and sirolimus and cyclosporine must be monitored. Often, patients will begin with a loading dose of sirolimus and then tapered to a lower dose. In patients considered at low risk for complications, cyclosporine may be weaned after 2-4 months and sirolimus concentrations increased.
Sirolimus is usually taken once a day at set intervals, with or without food. If cyclosporine is also being taken, then the dosages of both drugs should be separated by several hours. The sirolimus blood test is usually measured as a “trough” level, with blood collection just prior to the next dose – at the drug’s lowest concentration in the blood.
