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

• AimThe aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. MethodsNon-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5mg 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. ResultsThe apparent clearance rate (CL/F) and distribution volume (V/F) were 44l h(-1) 70kg(-1) and 236l 70kg(-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 t(max) and t(1/2) values were 1.65 (1.32-2.0) h and 2.60 (2.06-3.65) h, respectively. ConclusionsHere, 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

levamisole

nephrotic syndrome

population pharmacokinetics

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)