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Impact of ontogeny on linezolid disposition in neonates and infants

Gregory L Kearns1, Gail L Jungbluth, Susan M Abdel-Rahman

  • 1Division of Pediatric Pharmacology and Medical Toxicology, Children's Mercy Hospitals and Clinics, Kansas City, MO 64108, USA. gkearns@cmh.edu

Clinical Pharmacology and Therapeutics
|October 31, 2003
PubMed

Insights

Age significantly impacts linezolid clearance in newborns, with lower clearance observed in the first week of life. Gestational age is a key predictor of drug distribution in infants.

Area of Science:

  • Pharmacology
  • Neonatal Medicine
  • Drug Metabolism

Background:

  • The impact of infant age on linezolid pharmacokinetics is not well-established.
  • Understanding age-related drug disposition is crucial for optimizing pediatric dosing.

Purpose of the Study:

  • To characterize linezolid pharmacokinetics in neonates and young infants.
  • To investigate the influence of gestational and postnatal age on linezolid disposition.

Main Methods:

  • A single intravenous dose of linezolid (10.0 mg/kg) was administered to 42 infants.
  • Infants were stratified by gestational age (<34 vs. >=34 weeks) and postnatal age (<8 days vs. 8 days to 12 weeks).
  • Linezolid concentrations were measured using HPLC-triple-quadrupole mass spectrometry; pharmacokinetic parameters were determined using model-dependent methods.

Main Results:

  • Overall linezolid clearance (CL), volume of distribution (VD(ss)), and half-life (t(1/2)) were similar to those in older children.
  • CL increased rapidly with postnatal age, being significantly lower in infants <8 days old compared to those 8 days to 12 weeks old.
  • Gestational age was the primary predictor for VD(ss), while postnatal age influenced CL.

Conclusions:

  • Linezolid clearance is highly dependent on postnatal age, increasing significantly after the first week of life.
  • Gestational age is a critical factor for predicting linezolid volume of distribution in neonates.
  • Current linezolid dosing regimens approved for infants may be suitable for neonates older than 7 days.

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