Continuous Subcutaneous Delivery of Proline-Rich Antimicrobial Peptide Api137 Provides Superior Efficacy to Intravenous Administration in a Mouse Infection Model.

ABSTRACT: Apidaecins are cationic, proline-rich antimicrobial peptides originally isolated from honeybees and exhibit high Gram-negative activity by inhibiting bacterial protein translation. Pharmacokinetics of apidaecin derivative Api137 was studied using single and multiple intravenous or subcutaneous injections as well as continuous subcutaneous infusion and correlated to its efficacy in a lethal murine Escherichia coli infection model. Survival rates of infected CD-1 mice were monitored and Api137 and its metabolites were quantified in plasma of uninfected CD-1 mice and Sprague Dawley rats using reversed-phase chromatography coupled online to mass spectrometry. The highest Api137 plasma levels of 23 mg/L were obtained after a single intravenous injection of 20 mg/kg body weight, which declined f

SUBMITTER: Knappe D 

PROVIDER: S-EPMC6783563 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature