CYCLOSPORINE BLOOD LEVELS—AN EVALUATION OF RADIOIMMUNOASSAY WITH SELECTIVE MONOCLONAL OR POLYCLONAL ANTIBODIES AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY IN LIVER TRANSPLANT RECIPIENTS

Abstract

Cyclosporine blood levels were measured in 225 blood samples taken 14 days to 3 years after transplantation from 8 adult and 7 pediatric liver graft recipients. Results by high-performance liquid chromatography, radioimmunoassay with a polyclonal antibody (PARIA) or with a selective monoclonal antibody (MARIA) were compared in the context of major clinical events and alterations in serum bilirubin, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, urea, and creatinine. Cyclosporine blood levels by MARIA were significantly higher than HPLC values, but only by mean values of 11 μg/L in adult and 20 μg/L in pediatric patients. These differences were unaffected by alterations in liver or renal function and seem unlikely to affect clinical management. Minimum PARIA:HPLC ratios of 2–4 were noted in patients with good graft function, with higher ratios (up to 18) associated with hepatic dysfunction. Multiple regression analysis demonstrated that elevations in serum bilirubin and alkaline phosphatase significantly contributed toward the correlation with raised PARIA:HPLC ratios in adults and that γ-glutamyl transpeptidase and aspartate aminotransferase were additionally important in children. There was no significant contribution from either serum urea or creatinine levels to raised PARIA:HPLC ratios, but in children a positive correlation existed between these indicators of renal function and trough cyclosporine concentrations determined by selective methods (HPLC and MARIA).