Pharmacokinetic Outcomes of a Simplified, Weight‐Based, Extended‐Interval Gentamicin Dosing Protocol in Critically Ill Neonates

Hoff, David; Wilcox, Roger; Tollefson, Lisa M.; Lipnik, Polina G.; Commers, Amy R.; Liu, Meixia

doi:10.1592/phco.29.11.1297

Cited by 31 publications

(19 citation statements)

References 53 publications

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“…Unfortunately, PK data in adult patients on ECMO are sparse. Neonatal and animal studies are available but have shown significant variability and unpredictability of antibiotic PK during ECMO [32,35,46,50,[66][67][68][69][70][71][72][73][74][75][76][77][78][79] (Table 1). However, no dosing guidelines exist for this group of patients.…”

Section: Antibioticsmentioning

confidence: 99%

Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation

Shekar

Fraser

Smith

et al. 2012

Journal of Critical Care

280

315

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Section: Antibioticsmentioning

confidence: 99%

Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation

Shekar

Fraser

Smith

et al. 2012

Journal of Critical Care

280

315

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“…Drug metabolism is minimal as approximately 99% of the administered AGs are eliminated unaltered by glomerular filtration in the proximal tubule [34, 35]. The plasma half-life of AGs ranges from 1.5 to 3.5 hours [7, 36], but is prolonged in neonates, infants, and conditions with decreased kidney function [7, 37]. …”

Section: Pharmacokinetics and Antimicrobial Mechanism Of Aminoglycmentioning

confidence: 99%

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Huth

Ricci

Cheng

2011

International Journal of Otolaryngology

324

302

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Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.

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“…The mean gentamicin CL ranged from 0.028 to 0.07 L/hr/kg, the mean half-life ranged from 3.85 to 9.23 hours, and the mean or median central V D ranged from 0.39 to 0.98 L/kg [106–108,112]. In comparison, non-critically ill children had a mean CL of 0.042 L/hr/kg, mean half-life ranging from 2–8 hours, and a mean V D ranging from 0.3–0.43 L/kg [113,114].…”

Section: Pharmacokinetic Studies In Critically Ill Childrenmentioning

confidence: 99%

Clinical Pharmacology Studies in Critically Ill Children

et al. 2016

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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 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.

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Pharmacokinetic Outcomes of a Simplified, Weight‐Based, Extended‐Interval Gentamicin Dosing Protocol in Critically Ill Neonates

Cited by 31 publications

References 53 publications

Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation

Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

Clinical Pharmacology Studies in Critically Ill Children

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