A Phase 1 Study To Assess the Pharmacokinetics of Intravenous Plazomicin in Adult Subjects with Varying Degrees of Renal Function

Antimicrob Agents Chemother. 2018 Nov 26;62(12):e01128-18. doi: 10.1128/AAC.01128-18. Print 2018 Dec.

Abstract

Plazomicin is an FDA-approved aminoglycoside for the treatment of complicated urinary tract infections. In this open-label study, 24 adults with normal renal function or mild, moderate, or severe renal impairment (n = 6 per group) received a single 7.5-mg/kg of body weight dose of plazomicin as a 30-min intravenous infusion. Total clearance declined with renal impairment, resulting in 1.98-fold and 4.42-fold higher plazomicin exposures, as measured by the area under the concentration-time curve from 0 h to infinity, in subjects with moderate and severe impairment, respectively, than in subjects with normal renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT01462136.).

Keywords: aminoglycosides; antimicrobial agents; pharmacokinetics; renal impairment.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Area Under Curve
  • Drug Administration Schedule
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / pathogenicity
  • Enterobacteriaceae / physiology
  • Enterobacteriaceae Infections / blood
  • Enterobacteriaceae Infections / drug therapy*
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / physiopathology
  • Female
  • Humans
  • Infusions, Intravenous
  • Kidney / drug effects
  • Kidney / microbiology
  • Kidney / physiopathology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Renal Insufficiency / blood
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / microbiology
  • Renal Insufficiency / physiopathology
  • Severity of Illness Index
  • Sisomicin / analogs & derivatives*
  • Sisomicin / blood
  • Sisomicin / pharmacokinetics
  • Sisomicin / pharmacology
  • Urinary Tract Infections / blood
  • Urinary Tract Infections / drug therapy*
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / physiopathology

Substances

  • Anti-Bacterial Agents
  • plazomicin
  • Sisomicin

Associated data

  • ClinicalTrials.gov/NCT01462136