Evidence map›Paper›PMID 32720159›Full record

ArticlePharmaceutical research2020

Lymphatic Distribution of Etanercept Following Intravenous and Subcutaneous Delivery to Rats.

Xizhe Gao, Gregory Voronin, Claudia Generaux, Anne Rose, Alexander Kozhich, Gerard Dalglish, Raymond Rosa, Sarah Oh, Leonid Kagan

Abstract read
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Article in Pharmaceutical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

2 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. 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

9 authors at 2 institutions in 1 country.

Xizhe GaoDepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
Gregory VoroninComparative Medicine Resources, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Claudia GenerauxNonclinical Research and Development, Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Princeton, NJ, 08648, USA.
Anne RoseNonclinical Research and Development, Department of Pharmaceutical Candidate Optimization, Bristol Myers Squibb, Princeton, NJ, 08648, USA.
Alexander KozhichNonclinical Research and Development, Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, NJ, 08648, USA.
Gerard DalglishNonclinical Research and Development, Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, NJ, 08648, USA.
Raymond RosaComparative Medicine Resources, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Sarah OhDepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA.
Leonid KaganDepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854, USA. lkagan@pharmacy.rutgers.edu.ORCID http://orcid.org/0000-0003-3863-4757
Rutgers, The State University of New Jersey · USBristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe purpose of this work was to investigate the role of the lymphatic system in the pharmacokinetics of etanercept, a fusion protein.

methodsEtanercept 1 mg/kg was administered intravenously (IV) and subcutaneously (SC) to thoracic lymph duct-cannulated and sham-operated control rats. Blood and lymph samples were obtained for up to 6 days.

resultsModel-based SC bioavailability of etanercept was 65.2% in the control group. In lymph-cannulated rats, etanercept concentration in the lymph was consistently lower than in serum following IV dosing; and the concentration in the lymph was significantly higher than in serum after SC injection. The absorption occurred predominantly through the lymphatic pathway (82.7%), and only 17.3% by direct uptake into the central compartment (blood pathway). Lymphatic cannulation reduced the area under the serum concentration-time curve by 28% in IV group and by 91% in SC group. A mechanistic pharmacokinetic model that combined dual absorption pathways with redistribution of the systemically available protein drug into lymph was developed. The model successfully captured serum and lymph data in all groups simultaneously, and all parameters were estimated with sufficient precision.

conclusionsLymphatic system was shown to play an essential role in systemic disposition and SC absorption of etanercept.

Indexed as

CannulaAnimalsArea Under CurveBiological AvailabilityEtanerceptInjections, IntravenousInjections, SubcutaneousJugular VeinsLymphLymphatic SystemMaleModels, BiologicalRats, Sprague-DawleyThoracic DuctTime FactorsEtanerceptBiologicsBiotherapeuticsLymphatic drug absorptionModeling and simulationPK modelingProtein therapeutics

Identifiers

PMID32720159
OpenAlexW3044058019

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.