Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Bridging strategies for drug combinations in pediatric indications.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Comparative Study
  • Authors:
    Cella M, Danhof M, Della Pasqua O
  • Publication date:
  • Pagination:
    726, 733
  • Journal:
    Clin Pharmacol Ther
  • Volume:
  • Issue:
  • Status:
  • Country:
    United States
  • PII:
  • Language:
  • Keywords:
    Adolescent, Age Factors, Atovaquone, Child, Child, Preschool, Clinical Trials as Topic, Dose-Response Relationship, Drug, Drug Combinations, Female, Humans, Male, Proguanil, Randomized Controlled Trials as Topic, Registries
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.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by