RESUMO
AIM: The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. METHODS: Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg kg(-1) levamisole (or placebo) orally once every other day. One hundred and thirty-six plasma samples were collected from 38 children from India and Europe and included in the analysis. A one compartment model described the data well. RESULTS: The apparent clearance rate (CL/F) and distribution volume (V/F) were 44 l h(-1) 70 kg(-1) and 236 l 70 kg(-1) , respectively; estimated interindividual variability was 32-42%. In addition to allometric scaling of CL/F and V/F to body weight, we identified a significant proportional effect of age on CL/F (-10.1% per year). The pharmacokinetics parameters were not affected by gender, tablet strength or study centre. The median (interquartile range) maximum plasma concentration of levamisole was 438.3 (316.5-621.8) ng ml(-1) , and the median area under the concentration-time curve was 2847 (2267-3761) ng ml(-1) h. Median tmax and t½ values were 1.65 (1.32-2.0) h and 2.60 (2.06-3.65) h, respectively. CONCLUSIONS: Here, we present the first pharmacokinetic data regarding levamisole in children with steroid-sensitive nephrotic syndrome. The pharmacokinetic profile of levamisole in children was similar to findings reported in adults, although the elimination rate was slightly higher in children.