Everolimus

In addition to cyclosporine, tacrolimus, mycophenolic acid and sirolimus, everolimus (Certican®) has been introduced to the market in March 2004. In comparison to sirolimus, everolimus has better pharmacokinetics: a shorter half-life (28 h instead of 60 h), a slightly higher bioavailability, and a higher correlation of bioavailability with the administered dose. Everolimus is approved for the prevention of organ rejection after kidney and heart transplantations in combination with cyclosporine and corticosteroids.

Method
Demonstration by LC-MSMS (Tandem mass spectrometry after liquid chromatography)

Therapeutic range

3-8 ug/l trough level (temporary recommendation)
Concentrations exceeding 12 ug/l should be avoided.
Monitoring of the blood levels is particularly indicated if the patient is at the same time taking inductors (e.g. rifampicin, rifabutin) or inhibitors (e.g.ketoconazole, itraconazole, voriconazole, clarithromycin, telitromycin, ritonavir) of the cytochrome isoenzyme CYP-3A4, because everolimus is mainly metabolized along this way.
Enzymes of the CYP3A family are responsible for the metabolization of > 50% of all prescription drugs. Everolimus should also not be taken together with grapefruit juice since this juice can increase the bioavailability of various drugs by inhibition of the intestinal cytochrome P450-isoenzyme CYP3A4.

Pharmacokinetic data
Half-life: 28 hours
Peak level after oral administration: 1.3. to 1.8 hours
Steady State after 4 days.

Sample material
We need 0.5 ml EDTA whole blood (deep-frozen). The test is performed daily.

References
Kirchner Gl, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet. 2004; 43(2):83-95.
Armstrong VW, Streit F. Drug monitoring of Sirolimus and Everolimus. J Lab Med 2003; 27(5/6): 222-7