Determination of cyclosporine concentrations with monoclonal antibodies

We measured cyclosporine in whole blood from normal volunteers administered single oral doses of the drug and from two renal-transplant patients on immunosuppressive maintenance therapy, by liquid chromatography (I) and by radioimmunoassay with use of nonspecific polyclonal (II), specific monoclonal (III), and nonspecific monoclonal (IV) antibodies. Concentrations determined by III were equivalent to I, irrespective of cyclosporine dose, concentration, time after dose, or time after transplant. Concentrations determined by II and IV were consistently higher than those by I, owing to cross reactivity with metabolites. Ratios of values by II and IV to those by I increased from less than 1.5 to about 3-4 between 0.5 and 12 h after a single cyclosporine dose, owing to differences in rates of appearance and disappearance of cyclosporine and cross-reacting metabolites, though for the constant 12-h dose intervals in the two renal-transplant patients at steady state these ratios (most within the range 3-4) were relatively stable. Ratios of concentrations measured by IV to those by II (mean of 1.2 for single-dose data, most within the range of 1.2 to 1.5 at steady state) were unaffected by time after dose or time after transplant, suggesting that, despite certain cross-reactivity differences between the two nonspecific antibodies, results are proportional throughout therapy. We therefore propose that III and IV offer alternatives, respectively, to the currently used I and II for cyclosporine monitoring.