Pharmacokinetics and pharmacogenomics of β-lactam-induced neutropenia.

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.

• Authors: Andrea Hahn, Tsuyoshi Fukuda, David Hahn, Tomoyuki Mizuno, Robert W Frenck Jr, Alexander A Vinks
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 17 Issue 6 Pg. 547-59 (04 2016) ISSN: 1744-8042 [Electronic] England
• PMID: 27045542 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Multidrug Resistance-Associated Proteins
• Organic Anion Transporters, Sodium-Independent
• beta-Lactams

Topics

• Adolescent
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Male
• Multidrug Resistance-Associated Proteins (genetics)
• Neutropenia (chemically induced, genetics)
• Organic Anion Transporters, Sodium-Independent (genetics)
• Pharmacogenetics (methods)
• beta-Lactams (pharmacokinetics)