PHARMACOKINETICS OF CYCLOSPORINE AS A FUNCTION OF ENERGY-PROTEIN DEFICIENCY IN CHILDREN WITH CHRONIC-RENAL-FAILURE

The present study was conducted to determine whether malnutrition in p atients with chronic renal failure requiring cyclosporine therapy for renal transplantation has some effect on the clinical pharmacokinetics of cyclosporine. Eleven pediatric patients were enrolled in this stud y before renal transplantation and divided into two groups (group I: s ix well-nourished patients with a deficit in weight/height ratio less than or equal to 7%; group II: five malnourished patients with a defic it in weight/height > 8%). The patients received a single oral dose of cyclosporine (3.0 mg/kg). Blood samples were collected for a 26-hour period, and serum concentrations of cyclosporine were measured using f luorescence-polarization immunoassay technology. The results suggest t hat, when malnutrition is present, the median C-max of cyclosporine de creases by almost threefold (from 387.5 ng/mL in group I to 136.1 ng/m L in group II). An observed 52% reduction in AUC(0-infinity) (from 2,8 56.0 ng/mL/hr in group I to 1,481.4 ng/mL/hr in group II) was caused b y the increased volume of distribution (from 4.6 L/kg in group I to 11 .1 L/kg in group II). The elimination half-life (t(1/2)) was longer in group II compared with that of group I (12.4 hr for group II; range, 7.8-13.5 hr versus 8.9 hr for group I; range, 5.2-16.0 hr). Difference s in t(1/2) were not statistically significant at 5% confidence interv als. The effects of energy malnutrition on the pharmacokinetics of cyc losporine could explain in part some of the interindividual variabilit y. This study provides pharmacokinetic guidelines for the use of cyclo sporine.