A R Kreeftmeijer-Vegter1,2, T P C Dorlo1,3, M P Gruppen4, A de Boer1, P J de Vries2,5. 1. Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, P.O. Box 80 082, 3508 TB, Utrecht, the Netherlands. 2. ACE Pharmaceuticals BV, Schepenveld 41, 3891, ZK, Zeewolde, the Netherlands. 3. Department Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. 4. Department of Paediatric Nephrology, Emma Children's Hospital/Academic Medical Centre, Amsterdam, the Netherlands. 5. Department of Internal Medicine, Tergooi Ziekenhuis, Van Riebeeckweg 212, 1213 XZ, Hilversum, the Netherlands.
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.
RCT Entities:
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.
Authors: Angela Wolford; Thomas S McDonald; Heather Eng; Steven Hansel; Yue Chen; Jonathan Bauman; Raman Sharma; Amit S Kalgutkar Journal: Drug Metab Dispos Date: 2012-03-05 Impact factor: 3.922
Authors: M Luyckx; F Rousseau; M Cazin; C Brunet; J C Cazin; J M Haguenoer; B Devulder; I Lesieur; D Lesieur; P Gosselin; L Adenis; P Cappelaere; A Demaille Journal: Eur J Drug Metab Pharmacokinet Date: 1982 Oct-Dec Impact factor: 2.441
Authors: Annemarie Rosan Kreeftmeijer-Vegter; Mariska de Meijer; Kim A M Wegman; Cees K W van Veldhuizen Journal: Expert Opin Drug Deliv Date: 2013-01-05 Impact factor: 6.648