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Bridging strategies for drug combinations in pediatric indications.

Authors :
Cella M
Danhof M
Della Pasqua O
Source :
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2012 Apr; Vol. 91 (4), pp. 726-33. Date of Electronic Publication: 2012 Mar 07.
Publication Year :
2012

Abstract

Concurrent prescription of different drugs is common and is often necessary in many pediatric indications. A randomized concentration-controlled trial (RCCT) is proposed for pediatric studies in which drug combinations are used. The aim of our investigation was to show the relevance of flexible designs for accurate dose selection in such cases. We used the combination of atovaquone (ATV) and proguanil (PGN) as a paradigm to illustrate our approach. Pharmacokinetic models were developed for ATV and PGN using data pertaining to adults. The median area under the curve (AUC) in adults was considered the target exposure for bridging purposes. A pediatric population was simulated according to scenarios in which clearance varied from 20 to 100% of the reference adult values or allometrically correlated with body weight (BW). Doses were subsequently adapted according to the individual AUC estimates. Our results show that adaptive protocols are critical for accurate dose selection when evaluating drug combinations in children, ensuring that target exposure is achieved with respect to both active moieties in each individual patient.

Details

Language :
English
ISSN :
1532-6535
Volume :
91
Issue :
4
Database :
MEDLINE
Journal :
Clinical pharmacology and therapeutics
Publication Type :
Academic Journal
Accession number :
22398968
Full Text :
https://doi.org/10.1038/clpt.2011.298