Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome

Br J Clin Pharmacol. 2015 Aug;80(2):242-52. doi: 10.1111/bcp.12607. Epub 2015 Jun 5.

Abstract

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.

Keywords: levamisole; nephrotic syndrome; population pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / blood
  • Adjuvants, Immunologic / pharmacokinetics*
  • Adjuvants, Immunologic / therapeutic use
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / therapeutic use*
  • Age Factors
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Female
  • Humans
  • Levamisole / administration & dosage
  • Levamisole / blood
  • Levamisole / pharmacokinetics*
  • Levamisole / therapeutic use
  • Male
  • Models, Biological*
  • Nephrotic Syndrome / blood
  • Nephrotic Syndrome / drug therapy*
  • Recurrence

Substances

  • Adjuvants, Immunologic
  • Adrenal Cortex Hormones
  • Levamisole