Evidence map›Paper›PMID 30081725›Full record

ArticlemAbs2018

Minimal physiologically-based pharmacokinetic modeling of DSTA4637A, A novel THIOMAB™ antibody antibiotic conjugate against Staphylococcus aureus, in a mouse model.

Shun Xin Wang-Lin, Chenguang Zhou, Amrita V Kamath, Kyu Hong, Neelima Koppada, Ola M Saad, Montserrat Carrasco-Triguero, Cyrus Khojasteh, Rong Deng

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mAbs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
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  7. Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  8. Monoclonal antibody-based therapies for bacterial infections.Current opinion in infectious diseases · 2019
    Review
  9. Review
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

9 authors at 1 institution in 1 country.

Shun Xin Wang-Lina Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences , University at Buffalo, State University of New York , Buffalo , NY , USA.ORCID 0000-0002-2013-372X
Chenguang Zhoub Preclinical and Translational Pharmacokinetics, Genentech, Inc ., South San Francisco , CA , USA.
Amrita V Kamathb Preclinical and Translational Pharmacokinetics, Genentech, Inc ., South San Francisco , CA , USA.
Kyu Hongc Bioanalytical Sciences, Genentech, Inc ., South San Francisco , CA , USA.
Neelima Koppadac Bioanalytical Sciences, Genentech, Inc ., South San Francisco , CA , USA.
Ola M Saadc Bioanalytical Sciences, Genentech, Inc ., South San Francisco , CA , USA.ORCID 0000-0002-2607-8901
Montserrat Carrasco-Trigueroc Bioanalytical Sciences, Genentech, Inc ., South San Francisco , CA , USA.
Cyrus Khojastehd Drug Metabolism and Pharmacokinetics, Genentech, Inc ., South San Francisco , CA , USA.
Rong Denge Clinical Pharmacology, Genentech, Inc ., South San Francisco , CA , USA.
University at Buffalo, State University of New York · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DSTA4637A, a THIOMAB™ antibody-antibiotic conjugate targeting Staphylococcus aureus, has shown promising bactericidal activity in a mouse model. DSTA4637A consists of a monoclonal anti-S. aureus antibody with an average of two rifalogue antibiotic molecules, dmDNA31, linked to its light chains. The goal of this study was to develop a minimal physiologically-based pharmacokinetic (mPBPK) model to characterize the pharmacokinetic (PK) properties of three analytes of DSTA4637A (i.e., total antibody, antibody-conjugated dmDNA31, and unconjugated dmDNA31) in mice, and to predict pharmacokinetics of DSTA4637A analytes in humans, as well as to provide an initial assessment for potential PK drug-drug interactions (DDI) in clinical trials via cross-species scaling of the mPBPK model. In the proposed model, selected organs, including heart, liver, and kidney, were connected anatomically with plasma and lymph flows. Mouse plasma and tissue concentrations of the three analytes of DSTA4637A were fitted simultaneously to estimate the PK parameters. Cross-species scaling of the model was performed by integrating allometric scaling and human physiological parameters. The final mPBPK model was able to successfully capture PK profiles of three DSTA4637A analytes in mouse plasma and in investigated organs. The model predicted a steady-state peak unbound dmDNA31 concentration lower than 5% of the IC

Indexed as

AnimalsAnti-Bacterial AgentsAntibodies, BacterialAntibodies, MonoclonalDrug InteractionsFemaleHumansImmunoconjugatesMiceMice, SCIDModels, AnimalModels, BiologicalStaphylococcal InfectionsStaphylococcus aureusAnti-Bacterial AgentsAntibodies, BacterialAntibodies, MonoclonalImmunoconjugatescross-species scalingdrug-drug interactionsmPBPKStaphylococcus aureusTHIOMAB™ antibody antibiotic conjugate

Identifiers

PMID30081725
PMCPMC6204815
OpenAlexW2886341814

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.