Pharmacokinetics and Pharmacodynamics of Chemotherapy Drugs in Neonates and Infants

  • Carolina Witchmichen Penteado Schmidt


To briefly recall, pharmacokinetics involves absorption of a drug, binding of the drug to plasma proteins, biotransformation of the drug, and its excretion. Basically, pharmacokinetics involves the way that the drug goes through after it enters the body, whereas pharmacodynamics involves what the drug does in the body, i.e., the mechanism of action of the drug [1].


  1. 1.
    Schmidt CWP, Menezes FG. Drug therapy and interactions in pediatric oncology: a pocket guide. Switzerland: Springer; 2017.CrossRefGoogle Scholar
  2. 22.
    Lawrence CK, Smith PB. Dosing in neonates: special considerations in physiology and trial design. Pediatr Res. 2015;77:2–9.CrossRefGoogle Scholar
  3. 47.
    McLeod HL, Relling MV, Crom WR, et al. Disposition of antineoplastic drugs agents in the very young child. Br J Cancer Suppl. 1992;18:S23–9.PubMedPubMedCentralGoogle Scholar
  4. 23.
    Milsap RL, Jusko WJ. Pharmacokinetics in the infant. Environ Health Perspect. 1994;102(11):107–10.CrossRefGoogle Scholar
  5. 26.
    Fernandez E, Perez R, Hernandez A, et al. Factors and mechanisms for pharmacokinetic differences between pediatric population and adults. Pharmaceutics. 2011;3(1):53–72.CrossRefGoogle Scholar
  6. 25.
    Stephenson T. How children’s responses to drugs differ from adults. Br J Clin Pharmacol. 2005;59(6):670–3.CrossRefGoogle Scholar
  7. 53.
    Harvey RA, Mycek MJ. Farmacologia ilustrada. 5th ed. Porto Alegre: Artmed; 2013.Google Scholar
  8. 51.
    Piafsky KM. Disease-induced changes in the plasma binding of basic drugs. Clin Pharmacokinet. 1980;5(3):246–62.CrossRefGoogle Scholar
  9. 52.
    De Almeida JRC. Farmacêuticos em Oncologia: uma nova realidade. 2nd ed. São Paulo: Atheneu; 2010.Google Scholar
  10. 4.
    Taketomo C, Hodding J, Kraus D. Pediatric & neonatal dosage handbook. 21st ed. Hudson: Lexicomp; 2014.Google Scholar
  11. 48.
    Gitzelmann-Cumarasamy N, Gitzelmann R, Wilson KJ, Kuenzle CC. Fetal and adult albumins are indistinguishable by immunological and physiochemical criteria. Proc Natl Acad Sci U S A. 1979;76(6):2960–3.CrossRefGoogle Scholar
  12. 49.
    McNamara PJ, Alcorn J. Protein binding predictions in infants. AAPS Pharm Sci. 2002;4(1):19–26.CrossRefGoogle Scholar
  13. 50.
    Amin SB. Effect of free fatty acids on bilirubin–albumin binding affinity and unbound bilirubin in premature infants. JPEN J Parenter Enteral Nutr. 2010;34(4):414–20.CrossRefGoogle Scholar
  14. 24.
    Friis-Hansen BJ, Holiday M, Stapleton T, Wallace WM. Total body water in children. Pediatrics. 1951;7(3):321–7.PubMedGoogle Scholar
  15. 55.
    Lodish H, Berk A, Zipursky SL, et al. Molecular cell biology. 4th ed. New York: W. H. Freeman; 2000.Google Scholar
  16. 56.
    Li Q, Shu Y. Role of solute carriers in response to anticancer drugs. Mol Cell Ther. 2014;2:15. CrossRefGoogle Scholar
  17. 58.
    Lam J, Baello S, Iqbal M, et al. The ontogeny of P-glycoprotein in the developing human blood–brain barrier: implication for opioid toxicity in neonates. Pediatr Res. 2015;78:417–21.CrossRefGoogle Scholar
  18. 54.
    Yanagida O, Kanai Y, Chairoungdua A, et al. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001;1514(2):291–302.CrossRefGoogle Scholar
  19. 57.
    Hahn D, Emoto C, Vinks AA, Fukuda T. Developmental changes in hepatic organic cation transporter OCT1 protein expression from neonates to children. Drug Metab Dispos. 2017;45(1):23–6.CrossRefGoogle Scholar
  20. 67.
    Gow PJ, Ghabrial H, Smallwood RA, Morgan DJ, Ching MS. Neonatal hepatic drug elimination. Pharmacol Toxicol. 2001;88(1):3–15.CrossRefGoogle Scholar
  21. 60.
    Polin RA, Abman SH, Rowitch D, Benitz WE. Fetal and neonatal physiology. 5th ed. Philadelphia: Elsevier; 2017.Google Scholar
  22. 59.
    Law V, Knox C, Djoumbou Y, et al. DrugBank 4.0: shedding new light on drug metabolism.
  23. 61.
    Ligi I, Boubred F, Grandvuillemin I, Simeoni U. The neonatal kidney: implications for drug metabolism and elimination. Curr Drug Metab. 2013;14(2):174–7.PubMedGoogle Scholar
  24. 62.
    Sulemanji M, Vakili K. Neonatal renal physiology. Semin Pediatr Surg. 2013;22(2013):195–8.CrossRefGoogle Scholar
  25. 63.
    Boer DP, Rijke YB, Hop WC, et al. Reference values for serum creatinine in children younger than 1 year of age. Pediatr Nephrol. 2010;25(10):2107–13.CrossRefGoogle Scholar
  26. 64.
    Sato T, Takahashi N, Komatsu Y, et al. Urinary acidification in extremely low birth weight infants. Early Hum Dev. 2002;70(1-2):15–24.CrossRefGoogle Scholar
  27. 21.
    Tayman C, Rayyan M, Allegaert K. Neonatal pharmacology: extensive interindividual variability despite limited size. J Pediatr Pharmacol Ther. 2011;16(3):170–84.PubMedPubMedCentralGoogle Scholar
  28. 91.
    Brunton LL, Parker KL, Blumenthal DK, Bruxton ILO, editors. Goodman & Gilman: Manual de Farmacologia e Terapêutica. Porto Alegre: Artmed; 2010.Google Scholar
  29. 90.
    Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei cancer medicine. 6th ed. Hamilton: BC Decker; 2003.Google Scholar
  30. 68.
    Veal GJ, Errington J, Sastry J, et al. Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens. Cancer Chemother Pharmacol. 2016;77:685–92. CrossRefGoogle Scholar
  31. 71.
    Veal GJ, Errington J, Hayden J, et al. Carboplatin therapeutic monitoring in preterm and full-term neonates. Eur J Cancer. 2015;51(14):2022–30.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Carolina Witchmichen Penteado Schmidt
    • 1
  1. 1.CuritibaBrazil

Personalised recommendations