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. Method: 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 1 and clearance (CL) at 97.4 1.h(-1) (3.6 1.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 bioavailability of 85% of the 1-mg dose. Conclusion: 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.