title: Pharmacodynamic studies of cyclosporine in marrow transplant recipients. A comparison of three assay methods.
abstract: We investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft-versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.56 times higher than those measured by RIA. Ten patients developed renal dysfunction and 10 developed grades II-IV acute GVHD. Although univariate analysis showed that plasma CsA concentrations measured by either FPIA or RIA were significantly correlated with renal dysfunction, the association was stronger with FPIA. Plasma CsA concentrations measured by FPIA but not RIA remained a significant risk factor for renal dysfunction in a multivariate relative risk model. Amphotericin therapy was significantly associated with renal dysfunction in the univariate analysis but not in the multivariate analysis. No significant associations were found between whole blood CsA or CsA M1 concentration, patients' age, gender, or CsA dose and the risk of renal dysfunction. None of the covariates analyzed significantly correlated with the development of acute GVHD. These data suggest that plasma CsA concentrations measured by nonspecific assays may more accurately correlate with renal dysfunction than whole-blood CsA concentrations measured by HPLC in marrow transplant recipients.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: T R
authors.initials: TR
authors.lastname: McGuire
authors.forename: G C
authors.initials: GC
authors.lastname: Yee
authors.forename: S
authors.initials: S
authors.lastname: Emerson
authors.forename: D J
authors.initials: DJ
authors.lastname: Gmur
authors.forename: J
authors.initials: J
authors.lastname: Carlin
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D016231:Fluorescence Polarization Immunoassay / Q000379:methods*; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008875:Middle Aged; D011863:Radioimmunoassay / Q000379:methods*; D012307:Risk Factors
chemical_list: D016572:Cyclosporine