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European journal of clinical pharmacology
Nov, 2024;80 (11): 1807-1817.

Evaluation of pharmacokinetic target attainment and hematological toxicity of linezolid in pediatric patients.

Manal Abouelkheir, Maram R Aldawsari, Leen Ghonem, Aliyah Almomen, Emad Alsarhani, Sarah Alsubaie, Saeed Alqahtani, Zeyad Kurdee, Abdullah Alsultan
Author Information
  1. Manal Abouelkheir: Department of Clinical Pharmacy, Faculty of Pharmacy, Misr International University, Cairo, Egypt. manal.aboelkheir@miuegypt.edu.eg.
  2. Maram R Aldawsari: Department of Pharmacy, King Saud University Medical City, Riyadh, Saudi Arabia.
  3. Leen Ghonem: Department of Pharmacy, King Saud University Medical City, Riyadh, Saudi Arabia.
  4. Aliyah Almomen: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
  5. Emad Alsarhani: Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia.
  6. Sarah Alsubaie: Pediatric Infectious Disease Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  7. Saeed Alqahtani: Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia.
  8. Zeyad Kurdee: Clinical Biochemistry Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  9. Abdullah Alsultan: Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia. absultan@ksu.edu.sa.
PMID: 39183194 DOI: 10.1007/s00228-024-03740-3

Abstract

BACKGROUND: Linezolid is commonly used to treat severe and/or resistant Gram-positive infections. Few studies have assessed its pharmacokinetic (PK) target attainment in pediatrics.
OBJECTIVE: To evaluate the percentage of pediatrics achieving the PK targets of linezolid with standard dosing regimens and to assess the incidence and risk factors associated with its hematologic toxicity.
METHODS: This prospective observational study included pediatric patients aged 0-14 who received linezolid for suspected or proven Gram-positive infections. Linezolid trough concentrations and the 24-h area under the curve (AUC) were estimated, and hematologic toxicity was assessed.
RESULTS: Seventeen pediatric patients (5 neonates and 12 older pediatrics) were included. A wide variability was observed in linezolid's trough and AUC (ranging from 0.5 to 14.4 mg/L and from 86 to 700 mg.h/L, respectively). The median AUC was significantly higher in neonates than older pediatrics (436 [350-574] vs. 200 [134-272] mg,h/L, P���=���0.01). Out of all patients, only 41% achieved adequate drug exposure (AUC 160-300 mg.h/L and trough 2-7 mg/L), with 24% having subtherapeutic, and 35% having higher-than-optimal exposures. Hematological toxicity was observed in 53% of cases. Identified risk factors include treatment duration over 7 days, baseline platelet counts below 150��������10/L, sepsis/septic shock, and concomitant use of meropenem.
CONCLUSIONS: Linezolid's standard dosing failed to achieve its PK targets in approximately half of our pediatric cohort. Our findings highlight the complex interplay between the risk factors of linezolid-associated hematological toxicity and underscore the importance of its vigilant use and monitoring, particularly in pediatrics with concomitant multiple risk factors.

Keywords

Drug exposure Hematologic toxicity Linezolid Pediatrics Pharmacokinetics

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MeSH Term

Humans
Linezolid
Infant
Child, Preschool
Child
Male
Female
Adolescent
Anti-Bacterial Agents
Infant, Newborn
Prospective Studies
Area Under Curve
Gram-Positive Bacterial Infections
Risk Factors

Chemicals

Linezolid
Anti-Bacterial Agents
Journal Article Observational Study
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0toxicitypediatricsriskfactorspediatricpatientsAUCLinezolidPKlinezolidtroughh/LGram-positiveinfectionsassessedpharmacokinetictargetattainmenttargetsstandarddosinghematologicincluded5neonatesolderobservedexposureconcomitantusehematologicalBACKGROUND:commonlyusedtreatsevereand/orresistantstudiesOBJECTIVE:evaluatepercentageachievingregimensassessincidenceassociatedMETHODS:prospectiveobservationalstudyaged0-14receivedsuspectedprovenconcentrations24-hareacurveestimatedRESULTS:Seventeen12widevariabilitylinezolid'sranging0144 mg/L86700 mgrespectivelymediansignificantlyhigher436[350-574]vs200[134-272]mgP���=���00141%achievedadequatedrug160-300 mg2-7 mg/L24%subtherapeutic35%higher-than-optimalexposuresHematological53%casesIdentifiedincludetreatmentduration7 daysbaselineplateletcounts150��������10/Lsepsis/septicshockmeropenemCONCLUSIONS:Linezolid'sfailedachieveapproximatelyhalfcohortfindingshighlightcomplexinterplaylinezolid-associatedunderscoreimportancevigilantmonitoringparticularlymultipleEvaluationDrugHematologicPediatricsPharmacokinetics

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