Evidence map›Paper›PMID 26451330›Full record

ArticleCPT: pharmacometrics & systems pharmacology2015

Physiologically Based Pharmacokinetic Model to Assess the Influence of Blinatumomab-Mediated Cytokine Elevations on Cytochrome P450 Enzyme Activity.

Y Xu, Y Hijazi, A Wolf, B Wu, Y-N Sun, M Zhu

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

Article in CPT: pharmacometrics & systems pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 6% 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

37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 66 citations in OpenAlex.

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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

6 authors at 2 institutions in 2 countries.

Y XuAmgen, Clinical Pharmacology, Modeling and Simulation Group, Department of Medical Sciences Thousand Oaks, California, USA.
Y HijaziAmgen Research (Munich) Munich, Germany.
A WolfAmgen Research (Munich) Munich, Germany.
B WuAmgen, Clinical Pharmacology, Modeling and Simulation Group, Department of Medical Sciences Thousand Oaks, California, USA.
Y-N SunAmgen, Clinical Pharmacology, Modeling and Simulation Group, Department of Medical Sciences Thousand Oaks, California, USA.
M ZhuAmgen, Clinical Pharmacology, Modeling and Simulation Group, Department of Medical Sciences Thousand Oaks, California, USA.
Amgen (United States) · USAmgen (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Blinatumomab is a CD19/CD3 bispecific T-cell engager (BiTE®) antibody construct for treatment of leukemia. Transient elevation of cytokines (interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ)) has been observed within the first 48 hours of continuous intravenous blinatumomab infusion. In human hepatocytes, blinatumomab showed no effect on cytochrome P450 (CYP450) activities, whereas a cytokine cocktail showed suppression of CYP3A4, CYP1A2, and CYP2C9 activities. We developed a physiologically based pharmacokinetic (PBPK) model to evaluate the effect of transient elevation of cytokines, particularly IL-6, on CYP450 suppression. The predicted suppression of hepatic CYP450 activities was <30%, and IL-6-mediated changes in exposure to sensitive substrates of CYP3A4, CYP1A2, and CYP2C9 were <twofold and lasted <1 week. Model verification indicated that IL-6 was the key cytokine suppressing CYP450 activities; the duration of cytokine elevation was a major determinant of magnitude of suppression. This study shows the utility of PBPK modeling for risk assessment of cytokine-mediated drug interactions.

Identifiers

PMID26451330
PMCPMC4592530
OpenAlexW1880040018

What OpenQuestion holds

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Registered trials

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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.