title: Linezolid pharmacokinetics in pediatric patients: an overview.
abstract: BACKGROUND
  There are a number of physiologic and developmental differences between children and adults that can influence the absorption, distribution, metabolism and elimination of a drug. Therefore it is important to determine the specific pharmacokinetic characteristics for individual drugs in pediatric patients so that appropriate age-specific dosage regimens can be developed and evaluated in clinical trials. This review summarizes the pharmacokinetic parameters of linezolid in pediatric patients and the rationale for the approved dosing recommendations for this population.
  
  
  METHODS
  The pharmacokinetics of linezolid in pediatric patients has been evaluated in 4 clinical trials, including >180 patients ranging in age from preterm newborn infants up to 18 years of age. In all of these studies, patients received a single intravenous dose of linezolid. Plasma linezolid concentrations have been determined by validated high performance liquid chromatography (adult studies) or liquid chromatography/mass spectrometry/mass spectrometry (pediatric studies) methods.
  
  
  RESULTS
  The pharmacokinetics of linezolid, especially elimination clearance, is age-dependent. Children younger than 12 years of age have a smaller area under the drug concentration-time curve, a faster clearance and a shorter elimination half-life than adults. Although clearance rates in newborn infants are similar to those in adults, clearance increases rapidly during the first week of life, becoming 2- to 3-fold higher than in adults by the seventh day of life. The clearance of linezolid decreases gradually among young children, becoming similar to adult values by adolescence. The pharmacokinetics of linezolid in children age 12 years and older is not significantly different from that of adults.
  
  
  CONCLUSIONS
  Because of the higher clearance and lower area under the drug concentration-time curve, a shorter dosing interval for linezolid is required for children younger than 12 years of age to produce adequate drug exposure against target Gram-positive pathogens.
authors.affiliation: Clinical Pharmacology Unit, Pharmacia Corp., Kalamazoo, MI, USA
authors.forename: Gail L
authors.initials: GL
authors.lastname: Jungbluth
authors.forename: Ian R
authors.initials: IR
authors.lastname: Welshman
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Hopkins
mesh_terms: D000042:Absorption; D000081:Acetamides / Q000493:pharmacokinetics*; D000328:Adult; D000367:Age Factors; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D002986:Clinical Trials as Topic; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D000069349:Linezolid; D013058:Mass Spectrometry; D023303:Oxazolidinones / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid