Evidence map›Paper›PMID 34100188›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2021

A quantitative systems pharmacology model of hyporesponsiveness to erythropoietin in rats.

Ly Minh Nguyen, Zhichuan Li, Xiaoyu Yan, Wojciech Krzyzanski

Abstract read
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In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 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
0.6field-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, 5 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

4 authors at 2 institutions in 2 countries.

Ly Minh NguyenDepartment of Pharmaceutical Sciences, The State University of New York at Buffalo, 370 Pharmacy Building, New York, 14214, USA.
Zhichuan LiDepartment of Pharmaceutical Sciences, The State University of New York at Buffalo, 370 Pharmacy Building, New York, 14214, USA.
Xiaoyu YanSchool of Pharmacy, The Chinese University of Hong Kong, Hong Kong, China.
Wojciech KrzyzanskiDepartment of Pharmaceutical Sciences, The State University of New York at Buffalo, 370 Pharmacy Building, New York, 14214, USA. wk@buffalo.edu.ORCID 0000-0001-9773-1739
University at Buffalo, State University of New York · USChinese University of Hong Kong · HK

Funding

University Research Committee, University of Hong Kong (HK) grant 24103120
6 · The paper itself

Abstract

Recombinant human erythropoietin (rHuEPO) is effective in managing chronic kidney disease and chemotherapy-induced anemia. However, hyporesponsiveness to rHuEPO treatment was reported in about 10% of the patients. A decreased response in rats receiving a single or multiple doses of rHuEPO was also observed. In this study, we aimed to develop a quantitative systems pharmacology (QSP) model to examine hyporesponsiveness to rHuEPO in rats. Pharmacokinetic (PK) and pharmacodynamic (PD) data after a single intravenous dose of rHuEPO (100 IU/kg) was obtained from a previous study (Yan et al. in Pharm Res, 30:1026-1036, 2013) including rHuEPO plasma concentrations, erythroid precursors counts in femur bone marrow and spleen, reticulocytes (RETs), red blood cells (RBCs), and hemoglobin (HGB) in circulation. Parameter values were obtained from literature or calibrated with experimental data. Global sensitivity analysis and model-based simulations were performed to assess parameter sensitivity and hyporesponsiveness. The final QSP model adequately characterizes time courses of rHuEPO PK and nine PD endpoints in both control and treatment groups simultaneously. The model indicates that negative feedback regulation, neocytolysis, and depletion of erythroid precursors are major factors leading to hyporesponsiveness to rHuEPO treatment in rats.

Indexed as

AnemiaAnimalsBone MarrowErythrocytesErythropoietinEvaluation Studies as TopicHemoglobinsHumansMaleRatsRats, WistarRecombinant ProteinsRenal Insufficiency, ChronicReticulocytesSpleenEPO protein, humanErythropoietinHemoglobinsRecombinant ProteinsErythropoietinFeedback regulationHyporesponsivenessNeocytolysisPrecursor depletionSystems pharmacology model

Identifiers

PMID34100188
OpenAlexW3168961483

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.