Skip to main content
SpringerLink
Log in
Book cover

Pediatric Formulations pp 9–23Cite as

Pediatric Development: Physiology. Enzymes, Drug Metabolism, Pharmacokinetics and Pharmacodynamics

  • Chapter
  • First Online:

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 11))

Abstract

Growth and development consists of a continuum of biologic events that includes somatic growth, neurobehavioral maturation, and eventual reproduction, and has tremendous impact on the pharmacology of drugs in children. This impact is related to changes in body composition, development of organs and organ systems and change in these organs’ functions. Ontogeny is the science that studies the origin and development of an organism. Pharmacokinetics of drugs (what the body does to a drug) is summarized in the acronym ADME, which stands for absorption, distribution, metabolism, and elimination.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ADME:

Absorption, distribution, metabolism, elimination

BMI:

Body mass index

BSA:

Body surface area

CYP:

Cytochrome P450

ECW:

Extracellular water

FFM:

Fat-free mass

FM:

Fat mass

GFR:

Glomerular filtration rate

HAPMAP:

Haplotype map

ICW:

Intracellular water

PD:

Pharmacodynamics

P-gp:

P-glycoprotein

PGx:

Pharmacogenomics

PK:

Pharmacokinetics

TBW:

Total body weight

References

  1. Ahmad I, Nemet D, Eliakim A, Koeppel R, Grochow D, Coussens M, Gallitto S, Rich J, Pontello A, Leu S-Y et al (2010) Body composition and its components in preterm and term newborns: a cross-sectional, multimodal investigation. Am J Hum Biol 22:69–75

    Article  PubMed Central  PubMed  Google Scholar 

  2. Alcorn J, McNamara PJ (2003) Pharmacokinetics in the newborn. Adv Drug Deliv Rev 55:667–686

    Article  CAS  PubMed  Google Scholar 

  3. Atkinson M, Budge H (2011) Review of the NICE guidance on neonatal jaundice. Arch Dis Child Educ Pract Ed 96:136–140

    Article  CAS  PubMed  Google Scholar 

  4. Barrett DA, Rutter N (1994) Transdermal delivery and the premature neonate. Crit Rev Ther Drug Carrier Syst 11:1–30

    CAS  PubMed  Google Scholar 

  5. Bartelink IH, Rademaker CMA, Schobben AFAM, van den Anker JN (2006) Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet 45:1077–1097

    Article  CAS  PubMed  Google Scholar 

  6. Berseth CL (1996) Gastrointestinal motility in the neonate. Clin Perinatol 23:179–190

    CAS  PubMed  Google Scholar 

  7. Blake MJ, Gaedigk A, Pearce RE, Bomgaars LR, Christensen ML, Stowe C, James LP, Wilson JT, Kearns GL, Leeder JS (2007) Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clin Pharmacol Ther 81:510–516

    Article  CAS  PubMed  Google Scholar 

  8. Chen N, Aleksa K, Woodland C, Rieder M, Koren G (2006) Ontogeny of drug elimination by the human kidney. Pediatr Nephrol 21:160–168

    Article  PubMed  Google Scholar 

  9. Commare CE, Tappenden KA (2007) Development of the infant intestine: implications for nutrition support. Nutr Clin Pract 22:159–173

    Article  PubMed  Google Scholar 

  10. De Wildt SN, Kearns GL, Hop WCJ, Murry DJ, Abdel-Rahman SM, van den Anker JN (2002) Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol 53:390–392

    Article  PubMed  Google Scholar 

  11. Ellis KJ, Shypailo RJ, Abrams SA, Wong WW (2000) The reference child and adolescent models of body composition. A contemporary comparison. Ann N Y Acad Sci 904:374–382

    Article  CAS  PubMed  Google Scholar 

  12. Fomon SJ, Nelson SE (2002) Body composition of the male and female reference infants. Annu Rev Nutr 22:1–17

    Article  CAS  PubMed  Google Scholar 

  13. Ginsberg G, Hattis D, Sonawane B (2004) Incorporating pharmacokinetic differences between children and adults in assessing children’s risks to environmental toxicants. Toxicol Appl Pharmacol 198:164–183

    Article  CAS  PubMed  Google Scholar 

  14. Hines RN (2013) Developmental expression of drug metabolizing enzymes: impact on disposition in neonates and young children. Int J Pharm 452(1–2):3–7

    Google Scholar 

  15. Holford N (2010) Dosing in children. Clin Pharmacol Ther 87:367–370

    Article  CAS  PubMed  Google Scholar 

  16. Johnson TN, Thomson M (2008) Intestinal metabolism and transport of drugs in children: the effects of age and disease. J Pediatr Gastroenterol Nutr 47:3–10

    Article  CAS  PubMed  Google Scholar 

  17. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE (2003) Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med 349:1157–1167

    Article  CAS  PubMed  Google Scholar 

  18. Leeder JS, Kearns GL, Spielberg SP, van den Anker J (2010) Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science. J Clin Pharmacol 50:1377–1387

    Article  PubMed  Google Scholar 

  19. Murry DJ, Crom WR, Reddick WE, Bhargava R, Evans WE (1995) Liver volume as a determinant of drug clearance in children and adolescents. Drug Metab Dispos 23:1110–1116

    CAS  PubMed  Google Scholar 

  20. Pacifici GM (2009) Clinical pharmacokinetics of aminoglycosides in the neonate: a review. Eur J Clin Pharmacol 65:419–427

    Article  CAS  PubMed  Google Scholar 

  21. Saunders NR, Habgood MD, Dziegielewska KM (1999) Barrier mechanisms in the brain, II. Immature brain. Clin Exp Pharmacol Physiol 26:85–91

    Article  CAS  PubMed  Google Scholar 

  22. Seyberth HW, Kauffman RE (2011) Basics and dynamics of neonatal and pediatric pharmacology. Handb Exp Pharmacol 205:3–49

    Article  PubMed  Google Scholar 

  23. Tayman C, Rayyan M, Allegaert K (2011) Neonatal pharmacology: extensive interindividual variability despite limited size. J Pediatr Pharmacol Ther 16:170–184

    PubMed Central  PubMed  Google Scholar 

  24. Van den Anker JN, Schwab M, Kearns GL (2011) Developmental pharmacokinetics. Handb Exp Pharmacol 205:51–75

    Article  PubMed  Google Scholar 

  25. Ward RM, Tammara B, Sullivan SE, Stewart DL, Rath N, Meng X, Maguire MK, Comer GM (2010) Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD). Eur J Clin Pharmacol 66:555–561

    Article  CAS  PubMed  Google Scholar 

  26. Yaffe SJ, Aranda JV (2010) Neonatal and pediatric pharmacology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  27. Johnson CL, Versalovic (2012) The human microbiome and its potential importance to pediatrics. Pediatrics 129(5):950–60. doi: 10.1542/peds.2011-2736, Epub 2012 Apr 2

    Google Scholar 

  28. Wells A et al (2012) Body-composition reference data for simple and reference techniques and a 4-component model: a new UK reference child. Am J Clin Nutr 96(6):1316–1326

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Manitoba Institute of Child Health, 513-715 McDermot Avenue, Winnipeg, MB, Canada, R3E 3P4

    Geert ‘t Jong

Authors
  1. Geert ‘t Jong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Geert ‘t Jong .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutics Department of Analytical Chemistry, University of Copenhagen, Denmark

    Daniel Bar-Shalom

  2. Pediatric Drug Development & More, klausrose Consulting, Riehen, Switzerland

    Klaus Rose

Rights and permissions

Reprints and permissions

Copyright information

© 2014 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Jong, G.‘. (2014). Pediatric Development: Physiology. Enzymes, Drug Metabolism, Pharmacokinetics and Pharmacodynamics. In: Bar-Shalom, D., Rose, K. (eds) Pediatric Formulations. AAPS Advances in the Pharmaceutical Sciences Series, vol 11. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8011-3_2

Download citation

Publish with us

Policies and ethics

Search

Navigation