Specific monoclonal radioimmunoassay and fluorescence polarization immunoassay for trough concentration and area-under-the-curve monitoring of cyclosporine in renal transplantation.
In order to study the performance of a specific fluorescence polarization immunoassay (FPIA) for monitoring of the area under the concentration time curve (AUC) of cyclosporine (CsA), a total of 170 24-h CsA AUC studies were prospectively collected from 40 consecutive adult renal transplant recipients during the first 6 months after transplantation. Each AUC study included whole blood samples that had been collected at 0, 2, 4, 6, 10, 14, and 24 h after CsA administration. Each sample was subjected to CsA analysis in whole blood using a 3H-tracer specific monoclonal radioimmunoassay (wb-sRIA), specific FPIA (wb-sFPIA), and polyclonal FPIA (wb-pcFPIA). Furthermore, the performance of the specific assays was assessed against high-performance liquid chromatography (HPLC). Correlations between HPLC and specific assays were good, namely correlation coefficients of 0.94. Contrariwise, correlations between specific and nonspecific assay were poorer. As compared to HPLC, wb-sRIA overestimated CsA concentrations by 7.0%, and wb-sFPIA overestimated concentrations by 26.8%. The correlation between the AUC of CsA, as determined by wb-sRIA and wb-sFPIA, was excellent (r = 0.96). The ratio between wb-sFPIA and wb-sRIA was higher at low concentrations and small AUCs of CsA. On the average, CsA AUCs were 14% larger when assayed by wb-sFPIA. However, the appearance of the CsA concentration versus time curve was almost identical for the two assays. The apparent oral clearance (clearance/bioavailability) of CsA decreased with time after transplantation. Furthermore, the oral clearance of CsA was significantly higher in patients experiencing acute rejection than in those who were quiescent (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Lindholm
A
A
Department of Surgery, University of Texas Medical School, Houston 77030.
Napoli
K
K
Rutzky
L
L
Kahan
B D
BD
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D016231:Fluorescence Polarization Immunoassay / Q000379:methods; D006084:Graft Rejection / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008875:Middle Aged; D011446:Prospective Studies; D011863:Radioimmunoassay / Q000379:methods; D013997:Time Factors
D000911:Antibodies, Monoclonal; D016572:Cyclosporine