Ciclosporin (Blood)

Diagnostic Use

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

Liver Transplant C2  [ref 1]

Unit: ug/L

Heart Transplant C0   [ref 3]

Unit: ug/L

Lung Transplant  C0 and C2  [ref 4]

Unit: ug/L 

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.

Interpretation

See Diagnostic Use.

Reference Intervals

As a general guide, for whole blood samples where cyclosporin is used as the predominant immunosuppressant:

Units:  ug/L

(see under Diagnostic Use for more details)