Determining mycophenolate for monitoring transplantation

In addition to the immunosuppressive drugs cyclosporin A (Sandimune®) and tacrolimus (Prograf®, FK 506), mycophenolate mofetil is currently being used more and more often in combination therapy in order to prevent rejection reactions in renal transplants; its use with other organ transplants is being checked. Mycophenolate mofetil is converted in vivo to mycophenolate, the active immunosuppressant. Mycophenolate inhibits the de novo synthesis of purine (inhibition of inosine monophosphate dehydrogenase) and effects a blockage of the T and B lymphocyte population by means of a selective reduction of guanine nucleotides. This leads to a suppression of stronger immune reactions.

In the plasma compartment, mycophenolate is predominantly bound to proteins (binding to
albumin > 97 %). Other drugs that sometimes may be given at the same time, such as cyclosporine, prednisolone and tacrolimus, had no impact on plasma protein binding. Other compounds, such as tolbutamide, salicylic acid and furosemide can, however, significantly increase the proportion of free mycophenolate in the plasma. Mycophenolate is eliminated by being coupled to glucuronic acid; the metabolite is excreted via the biliary route. Due to an enterohepatic cycle, the result is a partial recirculation of the mycophenolate. This does not apply, however, for patients who are also receiving antibiotic therapy (e.g. bone marrow transplant patients; the lack of intestinal flora means that the glucuronide is not split).

Recommended dosage
See manufacturer’s recommendations; depends on the form of therapy and the transplant

Side effects
Diarrhoea can be observed initially; in such cases, the dose should then be reduced.

Test material
EDTA plasma, serum
Sample quantity: at least 1 ml
Shelf life: 7 days after centrifugation, storage at 2-8 °C

Therapeutic range
No general reference ranges have yet been identified.

With certain reservations, the following specifications apply: 1.8-3.0 µg/ml = mg/l for heart transplant patients and for some kidney transplant patients.
Values > 5 µl/ml are generally considered to be toxic.

To date, no interference has been observed in the test run due to increased bilirubin, triglyceride, cholesterol, haemoglobin or uric acid values.

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