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

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 d...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Abstracts
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752613/
http://dx.doi.org/10.1093/ofid/ofac492.1896
_version_ 1784850769878450176
author 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
author_facet 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
author_sort Bhavnani, Sujata M
collection PubMed
description 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 relevant covariates were identified. As shown in Figures A and B for plasma and ELF, respectively, the PTA was ≥ 90% for pathogens with an MIC ≤ 4 µg/mL across renal function categories in simulated patients, using PK/PD targets associated with a 1-log kill(10). No relationships were observed between PK/PD indices and efficacy endpoints, consistent with most patients achieving SUL and DUR exposures above nonclinical PK/PD targets for efficacy. Percent PTA by MIC on Day 1 based on the assessment of sulbactam %T>MIC ≥ 50% and durlobactam AUC:MIC ratio ≥ 10 targets and free-drug plasma (A) and total-drug ELF (B) exposures among simulated patients by CLcr group after administration of sulbactam 1 g/ durlobactam 1 g IV q6h and dosing regimens adjusted for renal impairment and augmented renal function [Figure: see text] CONCLUSION: The simulated plasma and ELF exposures yielded a high PTA, which when combined with the favorable efficacy and safety findings from ATTACK (abstract #1266378), support a dose of 1.0 g sulbactam/1.0 g durlobactam via a 3-hour infusion, every 6 hours in patients with normal renal function and renal function-based dose adjustments. DISCLOSURES: Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Christopher M. Rubino, PharmD, Adagio Therapeutics: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Jeffrey P. Hammel, MS, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Anthony P. Cammarata, M.S., Adagio Therapeutics, Inc: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Kajal Larson, PhD, Entasis Therapeutics: Employee Kathryn Liolios, MA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sarah McLeod, PhD, Entasis Therapeutics: Employee Alita Miller, PhD, Entasis Therapeutics: Employee Paul G. Ambrose, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Ruben Tommasi, PhD, Entasis Therapeutics: Employee John O'Donnell, B.S, Entasis Therapeutics: Employee
format Online
Article
Text
id pubmed-9752613
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-97526132022-12-16 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 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 Open Forum Infect Dis Abstracts 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 relevant covariates were identified. As shown in Figures A and B for plasma and ELF, respectively, the PTA was ≥ 90% for pathogens with an MIC ≤ 4 µg/mL across renal function categories in simulated patients, using PK/PD targets associated with a 1-log kill(10). No relationships were observed between PK/PD indices and efficacy endpoints, consistent with most patients achieving SUL and DUR exposures above nonclinical PK/PD targets for efficacy. Percent PTA by MIC on Day 1 based on the assessment of sulbactam %T>MIC ≥ 50% and durlobactam AUC:MIC ratio ≥ 10 targets and free-drug plasma (A) and total-drug ELF (B) exposures among simulated patients by CLcr group after administration of sulbactam 1 g/ durlobactam 1 g IV q6h and dosing regimens adjusted for renal impairment and augmented renal function [Figure: see text] CONCLUSION: The simulated plasma and ELF exposures yielded a high PTA, which when combined with the favorable efficacy and safety findings from ATTACK (abstract #1266378), support a dose of 1.0 g sulbactam/1.0 g durlobactam via a 3-hour infusion, every 6 hours in patients with normal renal function and renal function-based dose adjustments. DISCLOSURES: Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Christopher M. Rubino, PharmD, Adagio Therapeutics: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Jeffrey P. Hammel, MS, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Anthony P. Cammarata, M.S., Adagio Therapeutics, Inc: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Kajal Larson, PhD, Entasis Therapeutics: Employee Kathryn Liolios, MA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Sarah McLeod, PhD, Entasis Therapeutics: Employee Alita Miller, PhD, Entasis Therapeutics: Employee Paul G. Ambrose, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|ICPD Holdings: Ownership Interest|ICPD Technologies: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support Ruben Tommasi, PhD, Entasis Therapeutics: Employee John O'Donnell, B.S, Entasis Therapeutics: Employee Oxford University Press 2022-12-15 /pmc/articles/PMC9752613/ http://dx.doi.org/10.1093/ofid/ofac492.1896 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstracts
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
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752613/
http://dx.doi.org/10.1093/ofid/ofac492.1896
work_keys_str_mv AT bhavnanisujatam lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT bhavnanisujatam lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT bhavnanisujatam lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT rubinochristopherm lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT hammeljeffreyp lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT cammarataanthonyp lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT larsonkajal lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT liolioskathryn lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT mcleodsarah lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT milleralita lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT ambrosepaulg lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT tommasiruben lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections
AT odonnelljohn lb2306populationpharmacokineticppkpharmacokineticpharmacodynamicattainmentptaandclinicalpharmacokineticpharmacodynamicpkpdanalysesforsulbactamdurlobactamsuldurtosupportdoseselectionforthetreatmentofacinetobacterbaumanniicalcoaceticuscomplexabcinfections

Ejemplares similares