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A Novel Formulation of Tigecycline Has Enhanced Stability and Sustained Antibacterial and Antileukemic Activity
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A Novel Formulation of Tigecycline Has Enhanced Stability and Sustained Antibacterial and Antileukemic Activity
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Journal Article
A Novel Formulation of Tigecycline Has Enhanced Stability and Sustained Antibacterial and Antileukemic Activity
2014
Overview
Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin and intra-abdominal infections, as well as community-acquired pneumonia. In addition, we have demonstrated that tigecycline also has in vitro and in vivo activity against acute myeloid leukemia (AML) due to its ability to inhibit mitochondrial translation. Tigecycline is relatively unstable after reconstitution, and this instability may limit the use of the drug in ambulatory infusions for the treatment of infection and may prevent the development of optimal dosing schedules for the treatment of AML. This study sought to identify a formulation that improved the stability of the drug after reconstitution and maintained its antimicrobial and antileukemic activity. A panel of chemical additives was tested to identify excipients that enhanced the stability of tigecycline in solution at room temperature for up to one week. We identified a novel formulation containing the oxygen-reducing agents ascorbic acid (3 mg/mL) and pyruvate (60 mg/mL), in saline solution, pH 7.0, in which tigecycline (1 mg/mL) remained intact when protected from light for at least 7 days. This formulation also preserved the drug's antibacterial and antileukemic activity in vitro. Moreover, the novel formulation retained tigecycline's antileukemic activity in vivo. Thus, we identified and characterized a novel formulation for tigecycline that preserves its stability and efficacy after reconstitution.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Anti-Bacterial Agents - chemistry
/ Anti-Bacterial Agents - pharmacokinetics
/ Anti-Bacterial Agents - pharmacology
/ Cancer
/ Cell Survival - drug effects
/ Chromatography, High Pressure Liquid
/ Humans
/ Leukemia
/ Leukemia, Myeloid, Acute - drug therapy
/ Medicine and Health Sciences
/ Mice
/ Minocycline - analogs & derivatives
/ Minocycline - pharmacokinetics
/ Minocycline - therapeutic use
/ Oxygen
/ Proteins
/ Skin
