Andrea Hahn1,2, Tsuyoshi Fukuda3,4, David Hahn3, Tomoyuki Mizuno3, Robert W Frenck4,5, Alexander A Vinks3,4. 1. Division of Infectious Disease, Children's National Medical Center, Washington, DC 200102, USA. 2. Department of Pediatrics, George Washington University School of Medicine, Washington, DC 200523, USA. 3. Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 452294, USA. 4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 452215, USA. 5. Division of Infectious Disease, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Abstract
AIM: Determine if individuals with β-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3. METHODS: 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. RESULTS: 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). CONCLUSION: MRP4 3348 A to G should be further studied for potential contribution to the development of β-lactam induced neutropenia.
AIM: Determine if individuals with β-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3. METHODS: 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. RESULTS: 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). CONCLUSION:MRP4 3348 A to G should be further studied for potential contribution to the development of β-lactam induced neutropenia.
Authors: Kelly Bleasby; Laura A Hall; Jennifer L Perry; Harvey W Mohrenweiser; John B Pritchard Journal: J Pharmacol Exp Ther Date: 2005-05-24 Impact factor: 4.030
Authors: Marc Ansari; Géraldine Sauty; Malgorzata Labuda; Vincent Gagné; Caroline Laverdière; Albert Moghrabi; Daniel Sinnett; Maja Krajinovic Journal: Blood Date: 2009-06-10 Impact factor: 22.113