Document Detail

Population pharmacokinetics of cefepime in the neonate.
MedLine Citation:
PMID:  15980347     Owner:  NLM     Status:  MEDLINE    
Newborn infants cared for in neonatal intensive care units may develop nosocomial infections. Cefepime, a "fourth-generation" cephalosporin (i.e., with activity against virtually all of the chromosomal-beta-lactamase-producing and many extended-spectrum-beta-lactamase-producing organisms), provides excellent activity against many gram-negative pathogens resistant to expanded-spectrum cephalosporins currently used to treat neonatal infections. The purpose of this study was to determine the pharmacokinetics of cefepime in this population to optimize dosing and minimize potential adverse events. Premature and term infants <4 months of age hospitalized in two neonatal intensive care units were studied. Limited pharmacokinetic (PK) sampling occurred following a dose of cefepime at 50 mg/kg of body weight infused over 30 min. Population pharmacokinetic parameters were determined using the program NONMEM. Fifty-five infants were enrolled. Their average (+/- standard deviation) gestational age at birth was 30.5 +/- 5.3 weeks, and their average postnatal age at PK evaluation was 14.5 +/- 14.7 days. In the final PK model, cefepime clearance (CL) was strongly associated with serum creatinine (SCr) (CL [ml/min/kg] = 0.26 + 0.59/SCr). The volume of distribution for infants with a postconceptional age of <30 weeks was larger than that for infants with a postconceptional age of >30 weeks (0.51 versus 0.39 liter/kg, respectively). The Bayesian analysis-predicted cefepime trough concentration at a dose of 50 mg/kg every 12 h for infants < or = 14 days of age was 29.9 +/- 16.6 microg/ml. Cefepime, dosed at 30 mg/kg/dose every 12 h for infants less than 14 days of age, regardless of gestational age, should provide antibiotic exposure equivalent to or greater than 50 mg/kg every 8 h in older infants and children.
Edmund Capparelli; Christine Hochwald; Maynard Rasmussen; Amy Parham; John Bradley; Fernando Moya
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  49     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-27     Completed Date:  2005-08-19     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2760-6     Citation Subset:  IM    
Pediatric Pharmacology Research Unit, University of California, 4094 4th Avenue, Suite 201, San Diego, California 92103, USA.
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MeSH Terms
Anti-Bacterial Agents / administration & dosage,  blood,  pharmacokinetics*
Cephalosporins / administration & dosage,  blood,  pharmacology*
Creatinine / blood
Gestational Age
Infant, Newborn
Infant, Premature
Infusions, Intravenous
Intensive Care Units, Neonatal
Grant Support
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Cephalosporins; 60-27-5/Creatinine; 88040-23-7/cefepime

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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