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:
-
5 days at 15-25 o C
-
7 days at 2-8 o C
-
6 months at -20 o C
As a general guide, for whole blood samples where cyclosporin is used as the predominant immunosuppressant:
Units: ug/L
|
Trough range: 160 - 360 |
(see under Diagnostic Use for more details)
Uncertainty of Measurement:
12%
Assay performed every day, but specimen must arrive at the
testing
laboratory no later than 1400
for the result to be available on the same day.
Usually available by 1600
.
Urgent requests may be able to be processed
at other times following a telephone request
Principle: Competitive type immunoassay with chemiluminescence detection
Reagents: Roche Cyclosporine
Analyser: Cobas e801
Cyclosporin is an immunosuppressive agent which selectively inhibits T lymphocyte proliferation by blocking interleukin-2 synthesis. It is used for both primary immunosuppression and the treatment of allograft rejection.
There is a narrow therapeutic index and variable pharmacokinetics and so monitoring of therapy is strongly recommended.
Two strategies are used for monitoring, one based on trough sampling, i.e. the concentration of drug found within 1 hour before the next dose (termed C0), and the other on the concentration of drug found 2 hours after the dose is given (termed C2). C0 sampling has been widely used although it appears that C0 is only a weak indicator of absorption of drug. Moreover, the results are assay-dependent as samples of this type contain a large proportion of metabolite that may interfere. C2 sampling is advantageous in that C2 is an acceptable surrogate for absorption (measured as the area under the concentration-time curve). Moreover, most of the measured drug found at this time is parent drug, making the measurement relatively free of interference from metabolites. A disadvantage of C2 is the need for samples to be taken close to the 2-hour time-point (+ or -15 minutes).
The clinical usefulness of cyclosporin therapeutic drug monitoring for nontransplant indications like rheumatoid arthritis, severe psoriasis is still under debate . In general, dose of cyclosporin used for nontransplant autoimmune indications is lower than for transplant indications thus risk of e.g. nephrotoxicity is likely to be lower. Trough cyclosporin level (C0) may not correlate well with risk of nephrotoxicity. A very crude estimate of preferred C0 cyclosporin level (without too much evidence to base upon and may vary with different indications) is to aim for <200-250ug/L. The general recommendation is to adjust cyclosporin dose according to : serum creatinine monitoring - reduce if creatinine raised by >25-30% from baseline; monitoring of electrolytes like magnesium and lipid profile; blood pressure monitoring - hypertension (especially if not respond to usual antihypertensives); degree of clinical disease response
Factors affecting the target ranges for treatment include time of sampling (C0 or C2), organ transplanted, time since transplantation, and other medications. More specific recommended target concentrations for transplant patients are as follows. They may vary in individual cases on the basis of age, gender, renal function, number of episodes of rejection, and concomitant immunosuppressive medication.
Renal transplant C2 [ref 1]
These targets are for adults; equivalent concentrations in children (under 16 years) are lower but uncertain at the time of writing [ref 2].
Unit: ug/L
|
Time post transplant (months) |
Cyclosporin |
|---|---|
|
1 |
1700 |
|
2 |
1500 |
|
3 |
1300 |
|
4-6 |
1100 |
|
7-12 |
900 |
|
>12 |
800 |
Liver Transplant C2 [ref 1]
Unit: ug/L
|
Time post transplant (months) |
Cyclosporin |
|---|---|
|
0-3 |
1000 |
|
4-6 |
800 |
|
>6 |
600 |
Heart Transplant C0 [ref 3]
Unit: ug/L
|
Time post transplant (months) |
Cyclosporin |
|---|---|
|
0-1 |
300-350 |
|
1-6 |
200-300 |
|
6-12 |
175-250 |
|
>12 |
125-175 |
Lung Transplant C0 and C2 [ref 4]
Unit: ug/L
Time post transplant (months) 0-48 hours >300 >800 1-7 days 300-450 1200 1-4 weeks 300-450 1200-1700 2nd month 300-400 1000-1500 3rd month 300-400 800-1200 4-6 months 250-350 700-1000 7-12 months 200-300 600-900 >12 months (stable) 100-200 600-800 >12 months (renal impaired) 300-600
Cyclosporin (C0)
Cyclosporin (C2)
References:
1. Neoral C2 monitoring target levels. Novartis reference BSS 06.02.96, 2002.
2. William Wong, personal communication.
3. Peter Ruygrok, personal communication.
4. Tanya McWilliams, personal communication.
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
Whole blood is assayed. Specimens must NOT be separated and should be transported to the L aboratory as soon as possible. If necessary, they may be stored at 4C for up to 7 days prior to analysis. 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.