LB2306. Population Pharmacokinetic (PPK), Pharmacokinetic/Pharmacodynamic attainment (PTA), and Clinical Pharmacokinetic/Pharmacodynamic (PK/PD) Analyses for Sulbactam-Durlobactam (SUL-DUR) to Support Dose Selection for the Treatment of Acinetobacter baumannii-calcoaceticus Complex (ABC) Infections. (15th December 2022)

Record Type:: Journal Article
Title:: LB2306. Population Pharmacokinetic (PPK), Pharmacokinetic/Pharmacodynamic attainment (PTA), and Clinical Pharmacokinetic/Pharmacodynamic (PK/PD) Analyses for Sulbactam-Durlobactam (SUL-DUR) to Support Dose Selection for the Treatment of Acinetobacter baumannii-calcoaceticus Complex (ABC) Infections. (15th December 2022)
Main Title:: LB2306. Population Pharmacokinetic (PPK), Pharmacokinetic/Pharmacodynamic attainment (PTA), and Clinical Pharmacokinetic/Pharmacodynamic (PK/PD) Analyses for Sulbactam-Durlobactam (SUL-DUR) to Support Dose Selection for the Treatment of Acinetobacter baumannii-calcoaceticus Complex (ABC) Infections
Authors:: Bhavnani, Sujata M
Bhavnani, Sujata M
Bhavnani, Sujata M
Rubino, Christopher M
Hammel, Jeffrey P
Cammarata, Anthony P
Larson, Kajal
Liolios, Kathryn
McLeod, Sarah
Miller, Alita
Ambrose, Paul G
Tommasi, Ruben
O'Donnell, John
Abstract:: Abstract: Background: SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC infections, which are often severe and associated with substantial mortality. PPK, PTA, and clinical PK/PD analyses were conducted using all available PK and efficacy data to support SUL-DUR dose selection. Methods: PPK analyses were performed using PK data from 373 subjects, including 110 patients who received SUL-DUR and underwent PK sampling in the pivotal Phase 3 (ATTACK) trial. SUL-DUR concentrations in epithelial lining fluid (ELF) from healthy subjects were utilized to predict SUL-DUR ELF concentrations in Phase 3 patients. Covariate analyses evaluated the impact of demographic factors on PK exposures. The PPK model, non-clinical PK/PD data, and in vitro surveillance data were used to assess the PTA by MIC in simulated patients with ABC infections. Clinical PK/PD relationships were assessed using dichotomous and time-to-event efficacy endpoints from the ATTACK trial. Results: Two-compartment models with linear kinetics best characterized SUL and DUR PK. Consistent with high renal clearance of SUL-DUR, dose adjustments are needed in patients with renal impairment or augmented renal function. Body weight, site of infection, and East Asian region (which grouped patients from mainland China, Taiwan, and South Korea vs others) were statistically significant covariates in the PPK analysis but were not clinically relevant. No other statistical or clinically … (more)
Is Part Of:: Open forum infectious diseases. Volume 9:(2022)Supplement 2
Journal:: Open forum infectious diseases
Issue:: Volume 9:(2022)Supplement 2
Issue Display:: Volume 9, Issue 2 (2022)
Year:: 2022
Volume:: 9
Issue:: 2
Issue Sort Value:: 2022-0009-0002-0000
Page Start:
Page End:
Publication Date:: 2022-12-15
Subjects:: Communicable diseases -- Periodicals
Medical microbiology -- Periodicals
Infection -- Periodicals
616.9
Journal URLs:: http://ofid.oxfordjournals.org/ ↗
http://www.oxfordjournals.org/en/ ↗
DOI:: 10.1093/ofid/ofac492.1896 ↗
Languages:: English
ISSNs:: 2328-8957
Deposit Type:: Legaldeposit
View Content:: Available online (eLD content is only available in our Reading Rooms) ↗
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Ingest File:: 25181.xml