Journal Article

Penetration, efflux and intracellular activity of tigecycline in human polymorphonuclear neutrophils (PMNs)

Christine T. Ong, Chinedum P. Babalola, Charles H. Nightingale and David P. Nicolau

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 3, pages 498-501
Published in print September 2005 | ISSN: 0305-7453
Published online July 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki260
Penetration, efflux and intracellular activity of tigecycline in human polymorphonuclear neutrophils (PMNs)

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Objectives: To evaluate the penetration, efflux and intracellular activity of tigecycline in human polymorphonuclear neutrophils (PMNs).

Methods: PMNs were isolated from fresh whole blood and tested for viability and purity prior to use. Tigecycline drug uptake was evaluated by incubating 5 × 106 cells/mL at 37°C up to 3 h at tigecycline concentrations of 1, 2, 5 and 10 mg/L. Drug efflux from PMNs was determined following a 2 h incubation with tigecycline at 10 mg/L. Its intracellular activity against Staphylococcus aureus was evaluated following tigecycline extracellular exposures of 1 mg/L.

Results: Tigecycline uptake was rapid and achieved high concentrations within PMNs with maximal penetration noted at 1 h of incubation. At 1 h, dose-dependent intracellular concentrations ranged from 15.83 ± 11.09 mg/L to 264 ± 54.60 mg/L at tigecycline 1 and 10 mg/L, respectively. At these exposures, intracellular drug concentrations were ∼20 and 30 times higher at 1 h than extracellular concentrations. By 3 h, tigecycline displayed sustained high intracellular exposures. Tigecycline cell efflux followed first order kinetics with a half-life of 1.39 h. Tigecycline was bacteriostatic against intracellular S. aureus.

Conclusions: Tigecycline rapidly achieved high intracellular concentrations in PMNs and exhibited static activity against S. aureus supporting its potential clinical utilization.

Keywords: glycylcyclines; intracellular concentration; phagocytes

Journal Article.  2174 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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