EVIDENCE FOR PREHEPATIC METABOLISM OF ORAL CYCLOSPORINE IN CHILDREN

1 The pharmacokinetics of cyclosporine were investigated before renal transplantation in 20 children aged 1.1 to 16.8 years. Cyclosporine was given as a single oral dose (10 mg kg-1) or as a 4 h i.v. infusion (3 mg kg-1). 2 The blood drug concentration was measured by both specific and nonspecific monoclonal radioimmunoassays. 3 The mean oral availability of cyclosporine was 20.6% (range 10.8-34.1%). 4 The mean ratio of AUCs measured by nonspecific and specific r.i.a. was 1.96 (range 1.4-2.7) after oral administration and 1.43 (range 1.1-2.0) after i.v. administration. The mean difference between the ratios was 38.5% (P = 0.0001). The ratio of AUC(nonspecific) to AUC(specific) was inversely related to blood drug clearance (r = 0.57; P = 0.009). 5 The findings are suggestive of presystemic, pre-hepatic metabolism of cyclosporine which could contribute to the low, and highly variable bioavailability of this drug.