Evidence for pre-hepatic 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 AUCnonspecific to AUCspecific 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.
Hoppu
K
K
Children's Hospital, University of Helsinki, Finland.
Koskimies
O
O
Holmberg
C
C
Hirvisalo
E L
EL
D000284:Administration, Oral; D000293:Adolescent; D000367:Age Factors; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant
D016572:Cyclosporine