Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome
Kreeftmeijer-Vegter, A.R.; Dorlo, T.P.C.; Gruppen, M.P.; De Boer, A.; De Vries, P.J.
(2015) British Journal of Clinical Pharmacology, volume 80, issue 2, pp. 242 - 252
(Article)
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 2.5mg kg-1 levamisole (or placebo) orally once every other day.
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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 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 tmax and t1/2; 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.
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Keywords: levamisole, nephrotic syndrome, population pharmacokinetics, 2005-005745-18, prednisolone, prednisone, adolescent, area under the curve, article, body weight, child, clinical article, compartment model, controlled study, drug absorption, drug clearance, drug half life, elimination half-life, female, human, male, maximum plasma concentration, multicenter study (topic), plasma concentration-time curve, priority journal, randomized controlled trial (topic), relapse, remission, steroid sensitive nephrotic syndrome, time to maximum plasma concentration, volume of distribution, Taverne
ISSN: 0306-5251
Publisher: NLM (Medline)
(Peer reviewed)