PHARMACOKINETICS OF CYCLOSPORINE AFTER RENAL-TRANSPLANT IN CHILDREN

The pharmacokinetics of cyclosporine and the relationship between bloo d levels and average drug concentration were prospectively evaluated i n 18 children 1 month after renal transplantation. All children had no rmal renal function and no hepatic or gastrointestinal dysfunction. Cy closporine was administered after an overnight fast, and serial blood samples were drawn over a 24-hour period. Analysis of cyclosporine lev els was performed by means of monoclonal radio immunoassay on whole bl ood. Children were divided into three age groups for comparison: 2-5 y ears, 5-10 years, and >10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in th e pharmacokinetic para meters of cyclosporine except as follows: signi ficant differences were noted in cyclosporine dose based on body weigh t, apparent steady-stare volume of distribution, and apparent blood cl earance, with the youngest children (2-5) requiring higher doses, a re lative greater distribution, and exhibiting more rapid drug clearance than those >10 years of age, In addition, we observed diurnal variatio n in trough levels, with morning levels (0 hr) significantly higher th an those obtained in the evening (12 hours after administration of cyc losporine). Trough levels demonstrated a fair correlation with area un der the concentration-time curve (AUC) and average concentration (C-av ), but on abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.