Relationship between the dose and whole blood level of cyclosporine after liver and kidney transplantation

Descriptions of the immunosuppression protocols used after organ transplantation typically refer to the dose of cyclosporine (on a per weight basis) given to patients. In actual clinical practice, however, the amount of cyclosporine given to patients is determined principally by the concentration of the drug present in blood. In this study we determined the correlation between the dose of cyclosporine prescribed and the level of cyclosporine achieved in stable organ recipients three or more months following successful grafting. Seventy-five adult liver transplant recipients and 65 kidney transplant recipients who survived for more than three months after the transplant and who had stable graft function were included in the analysis. The cyclosporine dose and the cyclosporine level at the first out-patient visit were recorded for each patient. The median dose of cyclosporine used in liver recipients was 15 mg/kg/day. Seventeen percent of liver transplant recipients were on a maintenance dose of cyclosporine of less than 12 mg/kg/day. Fifteen percent were on a maintenance dose of greater than 22 mg/kg/day. The median dose utilized by kidney transplant recipients was 15 mg/kg/day. Twenty-eight percent of kidney recipients were on a maintenance dose of less than 12 mg/kg/day while 9% were taking more than 22 mg/kg/day. The median whole blood cyclosporine level in liver recipients was 1025 ng/ml (range 18-1925 ng/ml). The median level in kidney recipients was 542 ng/ml (range 79-1451 ng/ml). The majority of the liver and kidney recipients had cyclosporine levels within standard 'therapeutic' ranges reported for each type of transplant. However, one percent of liver recipients and 12% of kidney transplant recipients were maintaining normal allograft function despite levels of cyclosporine thought to have little or no immunosuppression effect. The liver transplant recipients who had a choledocho-choledo-chostomy had a median cyclosporine level of 948 ng/ml and were taking a median dose of cyclosporine of 14 mg/kg/day. In contrast liver transplant recipients with a Roux-Y choledocho-jejunostomy had a median cyclosporine level of 1024 ng/ml and were taking a median cyclosporine dose of 15 mg/k/day. This analysis demonstrates that the trough levels of cyclosporine achieved in blood does not correlate with the dose of cyclosporine administered to stable transplant recipients.