Steady-state concentration of cyclosporin G (OG37-325) and its metabolites in renal transplant recipients

Abstract The steady-state concentrations of cyclosporin G (OG37-325) (CsG) and six of its metabolites (GM1, GM9, GM4N, GM1c, GM1c9, GM19) were measured throughout the 12-h dosing interval in six renal transplant recipients receiving CsG as prophylaxis against acute cellular rejection. The mean 12-h whole-blood trough concentrations (micrograms/L) were CsG, 131 +/- 26; GM1, 79 +/- 55; GM9, 110 +/- 114; GM4N, 28 +/- 18; GM1c, 31 +/- 18; GM1c9, 216 +/- 145; and GM19, 303 +/- 217. The relative concentration of the primary metabolites (GM1, GM9, GM4N) remained stable with respect to CsG throughout the dosing interval, whereas that of the secondary metabolites increased. The secondary metabolites GM19 and GM1c9 exhibited extensive between-patient variation. We investigated the effect of these metabolites on commercially available monoclonal antibody-based fluorescence polarization immunoassays (FPIA) and RIAs adapted for measurement of CsG. The 12-h whole-blood trough concentrations measured by FPIA and RIA exceed those measured by HPLC by 19% and 36%, respectively. These measured biases corresponded closely with the calculated biases (FPIA 19%, RIA 28%) based on the known cross-reactivities of CsG metabolites and their concentrations. These results suggest that cross-reactivity with metabolites account for a large part of the bias observed in immunoassays of CsG.

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Abbott TDx monoclonal antibody assay evaluated for measuring cyclosporine in whole blood

Clinical Chemistry ◽

10.1093/clinchem/36.11.1969 ◽

1990 ◽

Vol 36 (11) ◽

pp. 1969-1973 ◽

Cited By ~ 64

Author(s):

R W Yatscoff ◽

K R Copeland ◽

C J Faraci

Keyword(s):

Monoclonal Antibody ◽

Renal Transplant ◽

Whole Blood ◽

Cross Reactivity ◽

The Other ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Antibody Assay ◽

Analytical Recovery ◽

Blood Specimens

Abstract We report here the evaluation of the Abbott TDx assay with a monoclonal antibody for selectively quantifying cyclosporine (CsA) in whole blood. Over the clinically relevant concentration ranges, results with this assay demonstrated within- and between-run CVs of less than 2.5% and 5%, respectively; sensitivity of 25 micrograms/L; good analytical recovery (100.3%); and linearity with whole-blood specimens. The percentage cross-reactivity of the major CsA metabolites varied from 15.3% for AM9 (M-1), 8.2% for AM1 (M-17), and 3.7% for AM4N (M-21), to less than 3% for the other metabolites tested. Results with the TDx assay (y) correlated well with those by the Sandimmune selective RIA (x; Sandoz) with blood specimens from 44 renal-transplant recipients (n = 44, x= 187.3, y = 198.9, y = 5.49 + 1.03x, r = 0.987). The TDx values were on average 24% higher than those by HPLC (x') with the same patients' specimens (n = 44, x' = 159.9, y = 198.9, y = 15.9 + 1.14x', r = 0.967). We conclude that the Abbott TDx monoclonal antibody assay provides a rapid, precise, and accurate means for quantifying CsA in whole blood.

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