Ketotifen pharmacokinetics in children with atopic perennial asthma.
OBJECTIVE
Published pharmacokinetic data on ketotifen are sparse, although it is a commonly used prophylactic agent in various allergic disorders in adults and children. The aim of this study was to assess the steady-state pharmacokinetics of ketotifen in children with atopic perennial asthma who were participating in a clinical trial.


METHODS
The NONMEM population approach with sparse sampling was utilized. The data set consisted of 239 samples from 48 children who were randomized to receive either 1 mg or 2 mg oral ketotifen daily. Patients underwent a clinical examination and had a blood sample taken at 2-week intervals for 12 weeks. The ketotifen concentrations were measured by RIA.


RESULTS
A one-compartment model with first-order absorption was fit to the data. Volume was estimated at 394 l and clearance (CL) at 97.4 l.h-1 (3.6 l.h-1.kg-1). Weight or body surface area were the most influential covariates for explaining interindividual variability in CL. The 2-mg dose appeared to have a relative bio-availability of 85% of the 1-mg dose.


CONCLUSIONS
Children have a faster clearance of ketotifen than adults and would therefore require a higher dose per kilogram body weight to give comparable steady-state levels.
McFadyen
M L
ML
Pharmacology Department, University of Durban-Westville, South Africa. mcfadyen@pixie.udw.ac.za
Miller
R
R
Ludden
T M
TM
D018926:Anti-Allergic Agents / Q000493:pharmacokinetics*; D001249:Asthma / Q000150:complications / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000378:metabolism*; D007665:Ketotifen / Q000493:pharmacokinetics*
D018926:Anti-Allergic Agents; D007665:Ketotifen