Use of an integrated modelling and simulation approach to develop a simplified peginterferon alfa‐2a dosing regimen for children with hepatitis C

Aim The aim of the study was to simplify the dosing regimen of peginterferon alfa‐2a in paediatric patients with chronic hepatitis C. Methods A population pharmacokinetic (PK) model was developed using PK data from 14 children aged 2–8 years and 402 adults. Simulations were produced to identify a simplified dosing regimen that would provide exposures similar to those observed in the paediatric clinical trials and in the range known to be safe/efficacious in adults. Model predictions were evaluated against observed adult and paediatric data to reinforce confidence of the proposed dosing regimen. Results The final model was a two compartment model with a zero order resorption process. Covariates included a linear influence of body surface area (BSA) on apparent oral clearance (CL/ F ) and a linear influence of body weight on apparent volume of distribution of the central compartment ( V 1 / F ). A simplified dosing regimen was developed which is expected to provide exposures in children aged ≥5 years similar to the dosing formula used in the paediatric clinical trial and within the range that is safe/efficacious in adults. This simplified regimen is approved in the EU and in other countries for the treatment of chronic hepatitis C in treatment‐naive children/adolescents aged ≥5 years in combination with ribavirin. Conclusion Pre‐existing adult PK data were combined with relatively limited paediatric PK data to develop a PK model able to predict exposure in both populations adequately. This provided increased confidence in characterizing PK in children and helped in the development of a simplified dosing regimen of peginterferon alfa‐2a in paediatric patients.