Evidence map›Paper›PMID 42754780›Full record

ArticlePharmaceutical research2026

Physiologically Based Pharmacokinetic Modeling of Inhaled Polymyxin B: From Rabbit Optimization to Human Predictions.

Ramya Mahadevan, Shekhar Yeshwante, Rajnikant Sharma, Quentin Valle, ChunFu Cheng, Rani S Sellers, Maria Soledad Ramirez, Jian Li, Qi Tony Zhou, David Z D'Argenio and 1 more

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Ramya Mahadevan *Titus Family Department of Clinical Practice, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Shekhar Yeshwante *Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Rajnikant SharmaTitus Family Department of Clinical Practice, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Quentin ValleTitus Family Department of Clinical Practice, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
ChunFu ChengTitus Family Department of Clinical Practice, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA.
Rani S SellersLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Maria Soledad RamirezCenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA, USA.
Jian LiBiomedicine Discovery Institute, Infection Program, Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia.
Qi Tony ZhouDepartment of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, IN, USA.
David Z D'ArgenioAlfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
Gauri G RaoTitus Family Department of Clinical Practice, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA. gaurirao@usc.edu.ORCID http://orcid.org/0000-0002-8704-7770

Funding

Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases R01AI146160NHLBI Division of Intramural Research R01HL167828
6 · The paper itself

Abstract

objectivesDespite the potential of aerosolized polymyxin B (PMB) to enhance local lung exposure while minimizing nephrotoxicity in multidrug-resistant pneumonia, clinical adoption remains limited by insufficient inhaled pharmacokinetic (PK) data. This study developed a physiologically based pharmacokinetic (PBPK) modeling framework to translate preclinical PK data from rabbits to humans and coupled it with a mechanism-based pharmacodynamic model to define optimal inhaled PMB regimens.

methodsA whole-body PBPK model was developed using plasma and tissue concentration data following subcutaneous and intratracheal PMB administration (2 mg/kg) in rabbits, extrapolated to humans using allometric scaling, and validated against clinical plasma and epithelial lining fluid (ELF) data. Monte Carlo simulations evaluated the probability of PK/PD target attainment (PTA) and probability of toxicity attainment (PToXA).

resultsIntratracheal administration achieved ~ 10.4-fold higher lung exposure relative to subcutaneous dosing while reducing kidney exposure by 27.7%. A plasma exposure threshold of 92.9 mg·h/L and a kidney tissue exposure threshold of 157 mg·h/L were identified as indicators of higher risk of AKI. Inhaled PMB monotherapy achieved favorable ELF PTA with 0% PToXA and predicted substantial bacterial load reduction (≥ 4 log

conclusionInhaled PMB provides superior site-specific exposure with minimal predicted nephrotoxicity. Our PBPK-mechanism-based modeling framework suggests that nebulized PMB rapidly clears bacteria while avoiding dose-limiting nephrotoxicity associated with intravenous therapy. These findings support advancing aerosolized PMB toward clinical implementation as a precision-dosing strategy for MDR pulmonary infections.

Indexed as

inhalationPBPKpolymyxin Brabbittranslational

Identifiers

PMID42754780

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.