Article

Improving pediatric dosing through pediatric initiatives: What we have learned

Food and Drug Administration, 5600 Fisher Lane, Parklawn Building, Room 13B-45, Rockville, MD 20850, USA.
PEDIATRICS (Impact Factor: 5.3). 03/2008; 121(3):530-9. DOI: 10.1542/peds.2007-1529
Source: PubMed

ABSTRACT The goal was to review the impact of pediatric drug studies, as measured by the improvement in pediatric dosing and other pertinent information captured in the drug labeling.
We reviewed the pediatric studies for 108 products submitted (July 1998 through October 2005) in response to a Food and Drug Administration written request for pediatric studies, and the subsequent labeling changes. We analyzed the dosing modifications and focused on drug clearance as an important parameter influencing pediatric dosing.
The first 108 drugs with new or revised pediatric labeling changes had dosing changes or pharmacokinetic information (n = 23), new safety information (n = 34), information concerning lack of efficacy (n = 19), new pediatric formulations (n = 12), and extended age limits (n = 77). A product might have had > or = 1 labeling change. We selected specific examples (n = 16) that illustrate significant differences in pediatric pharmacokinetics.
Critical changes in drug labeling for pediatric patients illustrate that unique pediatric dosing often is necessary, reflecting growth and maturational stages of pediatric patients. These changes provide evidence that pediatric dosing should not be determined by simply applying weight-based calculations to the adult dose. Drug clearance is highly variable in the pediatric population and is not readily predictable on the basis of adult information.

0 Followers
 · 
92 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nowadays the adjustment of medication for each patient is at the center of health strategy. Children can be considered as specific targets with their own specificities. In the oral route field some examples of drugs especially adapted to children can be found. Design is introduced in drug formulation to offer a better choice of products and now, children can be considered as partners in their own treatment. Enhanced comprehension of children's requirements can also lead to creation of drugs that improve compliance.
    12/2011; 1(1). DOI:10.3390/jpm1010005
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although both POPPK and physiologically based pharmacokinetic (PBPK) models can account for age and other covariates within a paediatric population, they generally do not account for real-time growth and maturation of the individuals through the time course of drug exposure; this may be significant in prolonged neonatal studies. The major objective of this study was to introduce age progression into a paediatric PBPK model, to allow for continuous updating of anatomical, physiological and biological processes in each individual subject over time. The Simcyp paediatric PBPK model simulator system parameters were reanalysed to assess the impact of re-defining the individual over the study period. A schedule for re-defining parameters within the Simcyp paediatric simulator, for each subject, over a prolonged study period, was devised to allow seamless prediction of pharmacokinetics (PK). The model was applied to predict concentration-time data from multiday studies on sildenafil and phenytoin performed in neonates. Among PBPK system parameters, CYP3A4 abundance was one of the fastest changing covariates and a 1-h re-sampling schedule was needed for babies below age 3.5 days in order to seamlessly predict PK (<5% change in abundance) with subject maturation. The re-sampling frequency decreased as age increased, reaching biweekly by 6 months of age. The PK of both sildenafil and phenytoin were predicted better at the end of a prolonged study period using the time varying vs fixed PBPK models. Paediatric PBPK models which account for time-varying system parameters during prolonged studies may provide more mechanistic PK predictions in neonates and infants.
    The AAPS Journal 04/2014; 16(3). DOI:10.1208/s12248-014-9592-9 · 3.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Modelling and simulation (M&S)-based approaches have been proposed to support paediatric drug development in order to design and analyze clinical studies efficiently. Development of anti-cancer drugs in the paediatric population is particularly challenging due to ethical and practical constraints. We aimed to review the application of M&S in the development of anti-cancer drugs in the paediatric population, and to identify where M&S-based approaches could provide additional support in paediatric drug development of anti-cancer drugs. A structured literature search on PubMed was performed. The majority of identified M&S-based studies aimed to use population PK modelling approaches to identify determinants of inter-individual variability, in order to optimize dosing regimens and to develop therapeutic drug monitoring strategies. Prospective applications of M&S approaches for PK-bridging studies have scarcely been reported for paediatric oncology. Based on recent developments of M&S in drug development there are several opportunities where M&S could support more informative bridging between children and adults, and increase efficiency of the design and analysis of paediatric clinical trials, which should ultimately lead to further optimization of drug treatment strategies in this population.
    British Journal of Clinical Pharmacology 07/2013; 76(1). DOI:10.1111/bcp.12062 · 3.69 Impact Factor