title: Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome.
abstract: OBJECTIVE
  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.
authors: Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, the Netherlands.|ACE Pharmaceuticals BV, Schepenveld 41, 3891, ZK, Zeewolde, the Netherlands.
authors: A R
authors: AR
authors: Kreeftmeijer-Vegter
authors: Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, the Netherlands.|Department Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors: T P C
authors: TP
authors: Dorlo
authors: Department of Paediatric Nephrology, Emma Children's Hospital/Academic Medical Centre, Amsterdam, the Netherlands.
authors: M P
authors: MP
authors: Gruppen
authors: Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, the Netherlands.
authors: A
authors: A
authors: de Boer
authors: ACE Pharmaceuticals BV, Schepenveld 41, 3891, ZK, Zeewolde, the Netherlands.|Department of Internal Medicine, Tergooi Ziekenhuis, Van Riebeeckweg 212, 1213 XZ, Hilversum, the Netherlands.
authors: P J
authors: PJ
authors: de Vries
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007978:Levamisole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D009404:Nephrotic Syndrome / Q000097:blood / Q000188:drug therapy*; D012008:Recurrence
chemical_list: D000276:Adjuvants, Immunologic; D000305:Adrenal Cortex Hormones; D007978:Levamisole
keywords: levamisole; nephrotic syndrome; population pharmacokinetics