title: Pharmacokinetics and pharmacogenomics of β-lactam-induced neutropenia.
abstract: Determine if individuals with β-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3.
  
  
  
  Subjects with β-lactam induced neutropenia were compared to controls for the presence of MRP4 and OAT1/OAT3 polymorphisms, estimated plasma trough concentrations and area under the curve.
  
  
  
  Subjects with a homozygous polymorphism at MRP4 3348 A to G were 5.3 times more likely to develop neutropenia (p = 0.171). No statistical differences were noted in pharmacokinetic parameters. Contingency analysis of children greater than 5 years of age showed neutropenia in subjects who were homozygous wild type at MRP4 3348 A to G was significantly associated with standard or high dosing (p = 0.03).
  
  
  
  MRP4 3348 A to G should be further studied for potential contribution to the development of β-lactam induced neutropenia.
authors.affiliation: Division of Infectious Disease, Children's National Medical Center, Washington, DC 200102, USA.|Department of Pediatrics, George Washington University School of Medicine, Washington, DC 200523, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 452294, USA.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 452215, USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 452294, USA.
authors.forename: David
authors.initials: D
authors.lastname: Hahn
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 452294, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 452215, USA.|Division of Infectious Disease, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Frenck
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 452294, USA.|Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 452215, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009503:Neutropenia / Q000139:chemically induced* / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods; D047090:beta-Lactams / Q000493:pharmacokinetics*
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029362:Organic Anion Transporters, Sodium-Independent; D047090:beta-Lactams
keywords: MRP4; OAT; neutropenia; β-lactam