title: Clinical Pharmacology Studies in Critically Ill Children.
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.
authors: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors: Nilay
authors: N
authors: Thakkar
authors: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Sara
authors: S
authors: Salerno
authors: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.|Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors: Christoph P
authors: CP
authors: Hornik
authors: Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. daniel.gonzalez@unc.edu.
authors: Daniel
authors: 0000-0001-5522-5686
authors: D
authors: Gonzalez
mesh_terms: D002648:Child; D016638:Critical Illness / Q000628:therapy*; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D010599:Pharmacokinetics; D010601:Pharmacology, Clinical / Q000379:methods; D017582:Renal Replacement Therapy / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations
keywords: clinical pharmacology; critically ill; organ dysfunction; pediatrics; pharmacokinetic alterations