Clinical Pharmacology Studies in Critically Ill Children

Nilay Thakkar, Sara Salerno, Christoph P. Hornik, Daniel Gonzalez

Research output: Contribution to journalReview article

  • 3 Citations

Abstract

Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this vulnerable population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs.

LanguageEnglish (US)
Pages7-24
Number of pages18
JournalPharmaceutical Research
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Clinical Pharmacology
Critical Illness
Pharmacokinetics
Pharmaceutical Preparations
Fluid Shifts
Pediatrics
Oxygenation
Extracorporeal Membrane Oxygenation
Renal Replacement Therapy
Multiple Organ Failure
Extrapolation
Vulnerable Populations
Tissue Distribution
Clinical Studies
Protein Binding
Tissue
Membranes
Fluids
Population

Keywords

  • clinical pharmacology
  • critically ill
  • organ dysfunction
  • pediatrics
  • pharmacokinetic alterations

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Clinical Pharmacology Studies in Critically Ill Children. / Thakkar, Nilay; Salerno, Sara; Hornik, Christoph P.; Gonzalez, Daniel.

In: Pharmaceutical Research, Vol. 34, No. 1, 01.01.2017, p. 7-24.

Research output: Contribution to journalReview article

Thakkar N, Salerno S, Hornik CP, Gonzalez D. Clinical Pharmacology Studies in Critically Ill Children. Pharmaceutical Research. 2017 Jan 1;34(1):7-24. Available from, DOI: 10.1007/s11095-016-2033-y
Thakkar, Nilay ; Salerno, Sara ; Hornik, Christoph P. ; Gonzalez, Daniel. / Clinical Pharmacology Studies in Critically Ill Children. In: Pharmaceutical Research. 2017 ; Vol. 34, No. 1. pp. 7-24
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