Relationship Between Everolimus Blood Concentration Assessed Using the Innofluor Certican Fluorescence Polarization Immunoassay and the Architect i System Sirolimus Chemiluminescent Microparticle Immunoassay

Abstract

Everolimus, an immunosuppressive macrolide derivative of sirolimus, has a narrow therapeutic index and variable bioavailability. Assessment of blood concentration of everolimus is necessary to improve immunosuppressive efficacy without increasing potential adverse effects. Recently, Seradyn, Inc (Indianapolis, Indiana) introduced a fluorescence polarization immunoassay (Innofluor Certican Fluorescent Polarization Immunoassay [FPIA]) for quantitation of everolimus blood concentration. This immunoassay has concentration-dependent cross-reactivity with sirolimus, which must be considered in patients recently treated with that drug. In this short-term study, treatment in 53 renal transplant recipients was converted from a sirolimus-based regimen to an everolimus-based regimen. Patients were followed up for 3 months. We investigated whether cross-reactivity with everolimus also occurred with the Abbott Laboratories (Abbott Park, Illinois) Architect i System, a sirolimus chemiluminescent microparticle immunoassay (CMIA) used to quantify sirolimus blood concentration. Quantification of everolimus blood concentration using both the CMIA and the FPIA demonstrated a linear regression: CMIA = 0.73 FPIA ± 0.77 ( r 2 = 0.80; P < .001). A high degree of correlation between the CMIA and FPIA methods ( r = 0.90) was confirmed using the Bland-Altman test. We conclude that the Abbott Architect i System sirolimus CMIA should be considered an alternative method for everolimus drug monitoring. The cross-reactions of both the FPIA and CMIA techniques with both sirolimus and everolimus must be considered when converting therapy from one drug to the other. In these conditions, use of an equivalent dosage is of particular importance.