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Review
. 2014 Aug 27:5:281.
doi: 10.3389/fgene.2014.00281. eCollection 2014.

Persistent pharmacokinetic challenges to pediatric drug development

Daniel P Sage  1 , Christopher Kulczar  1 , Wyatt Roth  1 , Wanqing Liu  2 , Gregory T Knipp  1
Affiliations
Review

Persistent pharmacokinetic challenges to pediatric drug development

Daniel P Sage et al. Front Genet. .

Abstract

The development of new therapeutic agents for the mitigation of pediatric disorders is largely hindered by the inability for investigators to assess pediatric pharmacokinetics (PK) in healthy patients due to substantial safety concerns. Pediatric patients are a clinical moving target for drug delivery due to changes in absorption, distribution, metabolism and excretion (ADME) and the potential for PK related toxicological (T) events to occur throughout development. These changes in ADMET can have profound effects on drug delivery, and may lead to toxic or sub-therapeutic outcomes. Ethical, economical, logistical, and technical barriers have resulted in insufficient investigation of these changes by industrial, regulatory, and academic bodies, leading to the classification of pediatric patients as therapeutic orphans. In response to these concerns, regulatory agencies have incentivized investigation into these ontogenic changes and their effects on drug delivery in pediatric populations. The intent of this review is to briefly present a synopsis of the development changes that occur in pediatric patients, discuss the effects of these changes on ADME and drug delivery strategies, highlight the hurdles that are still being faced, and present some opportunities to overcome these challenges.

Keywords: ADME; PBPK; ontogeny; pediatric; pharmacokinetic.

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References

    1. Abdel-Rahman S., Amidon G., Kaul A., Lukacova V., Vinks A., Knipp G., et al. (2012). Summary of the NICHD-BPCA Pediatric Formulation Initiatives Workshop- Pediatrics Biopharmaceutics Classification System (PBCS) Working Group. Clin. Ther. 34 S11–S24 10.1016/j.clinthera.2012.09.014 - DOI - PMC - PubMed
    1. Allegaert K., Smits A., van den Anker J. N. (2012). Physiologically based pharmacokinetic modeling in pediatric drug development: a clinician’s request for a more integrated approach. J. Biomed. Biotechnol. 2012 103763 10.1155/2012/103763 - DOI - PMC - PubMed
    1. Ansel H. C. (2010). Pharmaceutical Calculations. 13th Edn. Philadelphia, PA: Wolters Kluwer Health-Lippincott Williams and Wilkins; 121–22
    1. Baker-Smith C. M., Benjamin D. K., Jr., Grabowski H. G., Reid E. D., Mangum B., Goldsmith J. V., et al. (2008). The economic returns of pediatric clinical trials of antihypertensive drugs. Am. Heart J. 156 682–688 10.1016/j.ahj.2008.05.001 - DOI - PMC - PubMed
    1. Bartelink I. H., Rademaker C. M., Schobben A. F., van den Anker J. N. (2006). Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin. Pharmacokinet. 45 1077–1097 10.2165/00003088-200645110-00003 - DOI - PubMed

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