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

Abstract: 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 (V1/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.

Full Reference: Brennan, Barbara J., Annabelle Lemenuel-Diot, Eric Snoeck, Michael McKenna, Jonathan Solsky, Cynthia Wat, and Navita L. Mallalieu. “Use of an Integrated Modelling and Simulation Approach to Develop a Simplified Peginterferon Alfa-2a Dosing Regimen for Children with Hepatitis C.” British Journal of Clinical Pharmacology 81, no. 4 (April 2016): 658–66. doi:10.1111/bcp.12816.

Link to full text: http://onlinelibrary.wiley.com/doi/10.1111/bcp.12816/full

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