Sampling Optimisation in Pharmacokinetic Bridging Studies: Example on the Use of Deferiprone in Children With Β-Thalassaemia

Journal of Clinical Pharmacology
Francesco BellantiOscar Della Pasqua

Abstract

Despite the wide clinical experience with deferiprone, the optimum dosage in children aged less than 6 years remains to be established. This analysis is aimed at optimising the design of a prospective clinical study for the evaluation of deferiprone pharmacokinetics in children. A one-compartment model with first order oral absorption was used for the purposes of the analysis. Different sampling schemes were evaluated under the assumption of a constrained population size. A sampling scheme with 5 samples per subject was found to be sufficient to ensure accurate characterisation of the pharmacokinetics of deferiprone. Whereas the accuracy of parameters estimates was high, precision was slightly reduced due to the small sample size (> 30% for Vd/F and KA). AUC values (mean and SD) were found to be 33.37 (19.24) and 35.61 (20.22) mg/L.h and Cmax values 10.17 (6.05) and 10.94 (6.68) mg/L in sparse and frequent sampling, respectively. The results show that predefined sampling schemes and sample sizes do not warrant accurate model and parameter identifiability. ED-optimality and simulation-based optimisation concepts can be used to support PK bridging studies. Of importance is the accurate estimation of the magnitude of the covariate...Continue Reading

References

Feb 1, 1997·Pediatric Clinics of North America·O Diav-Citrin, G Koren
Jul 27, 2001·Journal of Pharmacokinetics and Pharmacodynamics·F MentréJ P Thénot
Jun 18, 2002·Blood Cells, Molecules & Diseases·Aurelio MaggioMassimo Midiri
Oct 29, 2002·Best Practice & Research. Clinical Haematology·John B Porter, Bernard A Davis
Feb 8, 2003·Annals of Biomedical Engineering·Andrew C HookerPaolo Vicini
Feb 28, 2004·Blood·Melody J CunninghamUNKNOWN Thalassemia Clinical Research Network
Mar 3, 2004·Computer Methods and Programs in Biomedicine·Marco ForacchiaAlfredo Ruggeri
Oct 6, 2005·Journal of Pharmacokinetics and Pharmacodynamics·Michael G DoddsPaolo Vicini
Nov 25, 2005·Journal of Pharmacokinetics and Pharmacodynamics·Timothy H WaterhouseJohn A Eccleston
Dec 13, 2005·Annals of the New York Academy of Sciences·C Borgna-PignattiA Cnaan
Apr 6, 2006·The AAPS Journal·Andrew Hooker, Paolo Vicini
Jun 30, 2006·European Journal of Pediatrics·Brian J AndersonNicholas H G Holford
Oct 31, 2007·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K Ogungbenro, L Aarons
Mar 6, 2008·British Journal of Clinical Pharmacology·Lie Michael George LimentaNoppawan Phumala Morales
May 17, 2008·European Journal of Clinical Pharmacology·Kayode Ogungbenro, Leon Aarons
Mar 26, 2009·Journal of Pharmacokinetics and Pharmacodynamics·Joakim NybergAndrew C Hooker
Oct 22, 2009·British Journal of Clinical Pharmacology·Efthymios Manolis, Gérard Pons
Oct 22, 2009·British Journal of Clinical Pharmacology·Kayode OgungbenroLeon Aarons
Nov 13, 2009·Acta Haematologica·R Galanello, S Campus
Jan 29, 2010·Clinical Pharmacology and Therapeutics·M CellaO Della Pasqua
Jun 2, 2010·Current Pharmaceutical Design·A D HenschelJ Boos
Aug 18, 2010·Annals of the New York Academy of Sciences·Antonio PigaFilomena Longo
Oct 6, 2010·Journal of Pediatric Hematology/oncology·Moshen S ElAlfyAmal El-Beshlawy
Nov 4, 2010·Journal of Pharmacokinetics and Pharmacodynamics·Marion Bouillon-PichaultMichel Tod
Nov 23, 2010·British Journal of Clinical Pharmacology·Massimo CellaOscar Della Pasqua
Dec 2, 2010·Expert Opinion on Drug Metabolism & Toxicology·Catherijne A J KnibbeMeindert Danhof
Dec 2, 2010·The Korean Journal of Hematology·Sung Chul WonChuhl Joo Lyu
Jan 20, 2011·Paediatric Anaesthesia·Efthymios ManolisAgnes Saint Raymond
Jan 20, 2011·European Journal of Clinical Pharmacology·Francesco Bellanti, Oscar Della Pasqua
Apr 20, 2011·British Journal of Clinical Pharmacology·Massimo CellaOscar Della Pasqua
Jul 16, 2011·The AAPS Journal·Peter GennemarkWarwick Tucker
Mar 29, 2012·Current Drug Metabolism·Elke H J KrekelsCatherijne A J Knibbe
May 30, 2012·Computer Methods and Programs in Biomedicine·Joakim NybergAndrew C Hooker
Dec 6, 2012·Clinical Pharmacokinetics·Cyrielle DumontMarylore Chenel
Feb 20, 2014·British Journal of Clinical Pharmacology·Joakim NybergFrance Mentré
Jul 24, 2014·British Journal of Clinical Pharmacology·Francesco BellantiOscar Della Pasqua

❮ Previous
Next ❯

Citations

Sep 20, 2016·British Journal of Clinical Pharmacology·Francesco BellantiUNKNOWN Consortium DEferiprone Evaluation in Paediatrics (DEEP)
Sep 28, 2016·The Journal of Pharmacy and Pharmacology·Eric VermeulenUNKNOWN Global Research in Paediatrics (GRiP)
Jul 18, 2019·European Journal of Clinical Pharmacology·Sven C van DijkmanOscar Della Pasqua

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.