Whole blood is assayed. Specimens must NOT be separated and should be transported to the Laboratory as soon as possible. If necessary, they may be stored at 4C for up to 7 days prior to analysis.
Sample stability:
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5 days at 15-25 o C
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7 days at 2-8 o C
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6 months at -20 o C
See diagnostic and interpretive notes below.
Assay performed every day, but specimen must arrive at the testing laboratory no later than 1400hr for the result to be available on the same day. Usually available by 1600hr.
Urgent requests may be able to be processed at other times following a telephone request.
Principle: Competitive type immunoassay with chemiluminescence detection
Reagents: Roche Sirolimus
Analyser: Cobas e801
Sirolimus is a macrocyclic lactone that inhibits cytokine induced T-lymphocyte proliferation, resulting in immunosuppression. It is used for prevention of kidney transplant rejection and for some other rare disorders.
Sirolimus has generally low, but variable, oral bioavailability and is rapidly absorbed from GI tract. It is metabolized in the intestine and liver (CYP3A and P-glycoprotein). It is mainly faecally excreted and liver impairment increases half-life.
Its half life in renal transplant patients also receiving ciclosporin and prednisone is around 60 hours, thus allowing once daily dosing.
Sirolimus should be administered 4 hours after ciclosporin due to increased risk of interaction. When initiating or discontinuing a ciclosporin regimen, sirolimus level should be carefully monitored.
Pre-dose trough level is recommended. Repeat sampling must not be taken until after the patient has been on a stable dose of sirolimus for at least 5-7days .
Sirolimus is mainly found in RBCs and a haemolysis preparation step is needed before assay.
When used with ciclosporin and corticosteroids, a trough whole blood therapeutic range of 5-15ug/L has been suggested. Without calcineurin inhibitors, a higher therapeutic interval 12-20ug/L has been suggested. After 12 months from transplant, lower target level may be appropriate.
Note, however, that these intervals are only meant for background reference. For individual patients with different drug-drug interactions, hepatic function and time since transplant, tailored therapeutic intervals as determined by the prescribing transplant specialist should be used.
Refs:
1. Dasgupta A. Therapeutic drug monitoring of Immunosuppressants in Resolving erroneous reports in toxicology and therapeutic drug monitoring ? a comprehensive guide.(2012) John Wiley & Sons, Inc.
2. Formea CM, Karlix JL. Antirejection agents in Clinical Pharmacokinetics (5 th edition) Murphy JE (ed) 2012 American Society of Health-System Pharmacists, Inc
3. Shah PR et al. Therapeutic drug monitoring of sirolimus. Clinical Queries: Nephrology 2015; 4:44-49
Uncertainty of Measurement: 18%
Emails to chemicalpathologist@adhb.govt.nz will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours : contact Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad (Clinical Lead) : SamarinaM@adhb.govt.nz ext. 22402
Dr Cam Kyle: CampbellK@adhb.govt.nz ext 22052
Dr Weldon Chiu: WeldonC@adhb.govt.nz ext. 23427
Dr Campbell Heron: CHeron@adhb.govt.nz ext. 23427
Dr Sakunthala Jayasinghe: Sakunthala@adhb.govt.nz ext. 23427
If the delay is going to be greater than 7 days, the sample must be stored at -20 C immediately after collection and transported frozen to the laboratory.