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Pharmacokinetics and pharmacogenomics of ?-lactam-induced neutropenia.

ABSTRACT: Determine if individuals with ?-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3.Subjects with ?-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 ?-lactam induced neutropenia.

SUBMITTER: Hahn A

PROVIDER: S-EPMC5558518 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Pharmacokinetics and pharmacogenomics of β-lactam-induced neutropenia.

Hahn Andrea A Fukuda Tsuyoshi T Hahn David D Mizuno Tomoyuki T Frenck Robert W RW Vinks Alexander A AA

Pharmacogenomics 20160405 6

<h4>Aim</h4>Determine if individuals with β-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3.<h4>Methods</h4>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.<h4>Results</h4>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 ...[more]

PMID: 27045542

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