Pharmacokinetics, safety, and tolerability of ceftibuten-ledaborbactam etzadroxil in participants with renal impairment
5 affiliations
- 1De Oliveira Consulting LLC, New Hope, Pennsylvania, USA
- 2Venatorx Pharmaceuticals, Inc., Malvern, Pennsylvania, USA
- 3Orlando Clinical Research Center, Orlando, Florida, USA
- 4Basilea Pharmaceutica International Ltd, Allschwil, Switzerland
- 5McGovern ID Consulting LLC, Berwyn, Pennsylvania, USA
Abstract
Ledaborbactam etzadroxil is an orally bioavailable prodrug of ledaborbactam, a broad-spectrum β-lactamase inhibitor being developed in combination with ceftibuten for the treatment of complicated urinary tract infections caused by antibiotic-resistant pathogens. As both agents are primarily eliminated via renal excretion, dose adjustment may be required in patients with impaired renal function. This phase 1 study (NCT05488678) evaluated the pharmacokinetics and safety of ceftibuten and ledaborbactam etzadroxil in participants with normal renal function; mild, moderate, or severe renal impairment; or end-stage renal disease (ESRD) undergoing hemodialysis. Participants received a single dose of ceftibuten-ledaborbactam etzadroxil (600 mg/600 mg); those with ESRD received doses both before and after hemodialysis. Among 32 enrolled participants, the mean age was 62.2 years, and 81.3% were male. For both ceftibuten and ledaborbactam, decreasing renal function was associated with increased plasma exposure and reduced renal clearance (CLr). In participants with mild, moderate, or severe renal impairment, plasma exposure of ceftibuten increased 1.3-, 2.3-, and 3.7-fold, respectively, and ledaborbactam increased 1.5-, 1.9-, and 4.4-fold, respectively. Ceftibuten CLr decreased from 2.2 L/h in participants with normal function to 0.3 L/h in those with severe impairment, while ledaborbactam CLr decreased from 3.0 to 0.5 L/h. In participants with ESRD, both drugs were moderately removed (23% and 38% for ceftibuten and ledaborbactam, respectively) by hemodialysis. No deaths, serious adverse events, or treatment-related adverse events leading to study drug discontinuation were reported. These results indicate that dose adjustment of ceftibuten-ledaborbactam etzadroxil will be required for patients with reduced renal function.This study is registered with ClinicalTrials.gov as NCT05488678.
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BibTeX
@article{oliveira2026pharmacokinetics,
title = {{Pharmacokinetics, safety, and tolerability of ceftibuten-ledaborbactam etzadroxil in participants with renal impairment}},
author = {Carlos Fernando de Oliveira and Kathryn Lowe and Penny Fatato and Thomas Marbury and Karine Litherland and Marc Engelhardt and Kamal A. Hamed and Paul C. McGovern},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = sep,
doi = {10.1128/aac.00860-26},
url = {https://doi.org/10.1128/aac.00860-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pharmacokinetics, safety, and tolerability of ceftibuten-ledaborbactam etzadroxil in participants with renal impairment
AU - Carlos Fernando de Oliveira
AU - Kathryn Lowe
AU - Penny Fatato
AU - Thomas Marbury
AU - Karine Litherland
AU - Marc Engelhardt
AU - Kamal A. Hamed
AU - Paul C. McGovern
PY - 2026
DA - 2026/09/28
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.00860-26
UR - https://doi.org/10.1128/aac.00860-26
AB - Ledaborbactam etzadroxil is an orally bioavailable prodrug of ledaborbactam, a broad-spectrum β-lactamase inhibitor being developed in combination with ceftibuten for the treatment of complicated urinary tract infections caused by antibiotic-resistant pathogens. As both agents are primarily eliminated via renal excretion, dose adjustment may be required in patients with impaired renal function. This phase 1 study (NCT05488678) evaluated the pharmacokinetics and safety of ceftibuten and ledaborbactam etzadroxil in participants with normal renal function; mild, moderate, or severe renal impairment; or end-stage renal disease (ESRD) undergoing hemodialysis. Participants received a single dose of ceftibuten-ledaborbactam etzadroxil (600 mg/600 mg); those with ESRD received doses both before and after hemodialysis. Among 32 enrolled participants, the mean age was 62.2 years, and 81.3% were male. For both ceftibuten and ledaborbactam, decreasing renal function was associated with increased plasma exposure and reduced renal clearance (CLr). In participants with mild, moderate, or severe renal impairment, plasma exposure of ceftibuten increased 1.3-, 2.3-, and 3.7-fold, respectively, and ledaborbactam increased 1.5-, 1.9-, and 4.4-fold, respectively. Ceftibuten CLr decreased from 2.2 L/h in participants with normal function to 0.3 L/h in those with severe impairment, while ledaborbactam CLr decreased from 3.0 to 0.5 L/h. In participants with ESRD, both drugs were moderately removed (23% and 38% for ceftibuten and ledaborbactam, respectively) by hemodialysis. No deaths, serious adverse events, or treatment-related adverse events leading to study drug discontinuation were reported. These results indicate that dose adjustment of ceftibuten-ledaborbactam etzadroxil will be required for patients with reduced renal function.This study is registered with ClinicalTrials.gov as NCT05488678.
SN - 1098-6596
SN - 0066-4804
ER -