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.

journal_name

Br J Clin Pharmacol

authors

Brennan BJ,Lemenuel-Diot A,Snoeck E,McKenna M,Solsky J,Wat C,Mallalieu NL

doi

10.1111/bcp.12816

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

658-66

issue

4

eissn

0306-5251

issn

1365-2125

journal_volume

81

pub_type

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