Evidence map›Paper›PMID 34433578›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2021

Semimechanistic Modeling of the Effects of Blast Overpressure Exposure on Cefazolin Pharmacokinetics in Mice.

Daniel J Selig, Geoffrey C Chin, Alexander G Bobrov, Jesse P DeLuca, Derese Getnet, Jeffrey R Livezey, Joseph B Long, Venkatasivasai S Sajja, Brett E Swierczewski, Stuart D Tyner and 1 more

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

Article in The Journal of pharmacology and experimental therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
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 at 2 institutions in 1 country.

Daniel J SeligWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.) daniel.j.selig.mil@mail.mil.
Geoffrey C ChinWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Alexander G BobrovWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Jesse P DeLucaWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Derese GetnetWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Jeffrey R LivezeyWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Joseph B LongWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Venkatasivasai S SajjaWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Brett E SwierczewskiWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Stuart D TynerWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Vlado AntonicWalter Reed Army Institute of Research, Silver Spring, Maryland, USA (D.J.S., G.C.C., A.G.B., J.P.D., D.G., J.B.L., V.S.S., B.E.S., S.D.T., V.A.); Uniformed Services University, Bethesda, Maryland, USA (J.R.L.).
Uniformed Services University of the Health Sciences · USWalter Reed Army Institute of Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cefazolin is a first-line antibiotic to treat infection related to deployment-associated blast injuries. Prior literature demonstrated a 331% increase cefazolin liver area under the curve (AUC) in mice exposed to a survivable blast compared with controls. We repeated the experiment, validated the findings, and established a semimechanistic two-compartment pharmacokinetic (PK) model with effect compartments representing the liver and skin. We found that blast statistically significantly increased the pseudo-partition coefficient to the liver by 326% (95% confidence interval: 76-737%), which corresponds to the observed 331% increase in cefazolin liver AUC described previously. To a lesser extent, plasma AUC in blasted mice increased 14-45% compared with controls. Nevertheless, the effects of blast on cefazolin PK were transient, normalizing by 10 hours after the dose. It is unclear as to how this blast effect t emporally translates to humans; however, given the short-lived effect on PK, there is insufficient evidence to recommend cefazolin dosing changes based on blast overpressure injury alone. Clinicians should be aware that cefazolin may cause drug-induced liver injury with a single dose and the risk may be higher in patients with blast overpressure injury based on our findings. SIGNIFICANCE STATEMENT: Blast exposure significantly, but transiently, alters cefazolin pharmacokinetics in mice. The questions of whether other medications or potential long-term consequences in humans need further exploration.

Indexed as

Models, BiologicalAnimalsAnti-Bacterial AgentsBlast InjuriesCefazolinChemical and Drug Induced Liver InjuryMaleMiceMice, Inbred BALB CPressureAnti-Bacterial AgentsCefazolin

Identifiers

PMID34433578
PMCPMC8626777
OpenAlexW3195311606

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.