title: Eravacycline Pharmacokinetics and Challenges in Defining Humanized Exposure In Vivo.
abstract: We assessed the pharmacokinetic profile of eravacycline, a novel antibiotic of the tetracycline class, and determined the dose in an immunocompetent murine thigh infection model that would provide free-drug exposure similar to that observed in humans after the administration of 1 mg/kg intravenously (i.v.) every 12 h (q12h). Eravacycline demonstrated a nonlinear protein-binding profile. The 2.5-mg/kg i.v. q12h dose in mice resulted in an area under the concentration-time curve for the free, unbound fraction of the drug of 1.64 mg · h/liter, which closely resembles the human exposure level.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Abrar K
authors.identifier: 0000-0002-0369-9094
authors.initials: AK
authors.lastname: Thabit
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors.forename: Marguerite L
authors.initials: ML
authors.lastname: Monogue
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA david.nicolau@hhchealth.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D013754:Tetracyclines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D013848:Thigh / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D013754:Tetracyclines; C571179:eravacycline