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.
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.
Authors: Kathleen B Schwarz; Regino P Gonzalez-Peralta; Karen F Murray; Jean P Molleston; Barbara A Haber; Maureen M Jonas; Philip Rosenthal; Parvathi Mohan; William F Balistreri; Michael R Narkewicz; Lesley Smith; Steven J Lobritto; Stephen Rossi; Alexandra Valsamakis; Zachary Goodman; Patricia R Robuck; Bruce A Barton Journal: Gastroenterology Date: 2010-10-28 Impact factor: 22.682
Authors: Kathleen B Schwarz; Parvathi Mohan; Michael R Narkewicz; Jean Pappas Molleston; S Russell Nash; Sylvia Hu; Ka Wang; Jean Michel Gries Journal: J Pediatr Gastroenterol Nutr Date: 2006-10 Impact factor: 2.839
Authors: Robert J Kuczmarski; Cynthia L Ogden; Shumei S Guo; Laurence M Grummer-Strawn; Katherine M Flegal; Zuguo Mei; Rong Wei; Lester R Curtin; Alex F Roche; Clifford L Johnson Journal: Vital Health Stat 11 Date: 2002-05
Authors: M Diago; J Crespo; A Olveira; R Pérez; R Bárcena; J M Sánchez-Tapias; M Muñoz-Sánchez; M Romero-Gómez Journal: Aliment Pharmacol Ther Date: 2007-10-15 Impact factor: 8.171