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Population pharmacokinetics and dosing optimization of latamoxef in neonates and young infants

Hui Qi1, Chen Kou2, Yu-Jie Qi3

  • 1Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

International Journal of Antimicrobial Agents
|November 26, 2018
PubMed

Insights

This study determined optimal latamoxef dosing for newborns, finding 30 mg/kg every 12 hours or 8 hours is effective based on pathogen. This provides evidence-based guidelines for treating neonatal infections with this historical antibiotic.

Area of Science:

  • Pharmacology
  • Neonatal Medicine
  • Infectious Diseases

Background:

  • Renewed interest in historical antibiotics due to rising antibiotic resistance.
  • Latamoxef, an oxacephem antibiotic, is used off-label in neonates without established dosing.
  • Need for evidence-based dosing regimens in neonatal clinical practice.

Purpose of the Study:

  • Evaluate latamoxef pharmacokinetics in neonates and young infants.
  • Establish an evidence-based dosing regimen for newborns.
  • Utilize developmental pharmacokinetics-pharmacodynamics (PK-PD) principles.

Main Methods:

  • Collected opportunistic blood samples from newborns treated with latamoxef.
  • Quantified latamoxef concentrations using high-performance liquid chromatography with UV detection.
  • Performed population PK-PD analysis with NONMEM and R software on 165 samples from 128 neonates.

Main Results:

  • A two-compartment model with first-order elimination best described latamoxef pharmacokinetics.
  • Body weight and postnatal age were significant covariates affecting latamoxef clearance.
  • Simulations showed 30 mg/kg q12h is adequate for MIC ≤ 1 mg/L; 30 mg/kg q8h is needed for MIC = 4 mg/L.

Conclusions:

  • Developmental PK-PD analysis supports rational dosing of latamoxef in newborns.
  • Recommended dosing regimens are 30 mg/kg every 12 hours or every 8 hours.
  • Dosing adjustments depend on the specific pathogen's minimum inhibitory concentration (MIC).
Abstract

Keywords:
LatamoxefNeonates and young infantsPharmacokinetics-pharmacodynamicsPopulation

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