Evidence map›Paper›PMID 23250851›Full record

ArticlePharmaceutical research2013

Pharmacokinetic and pharmacodynamic modeling of romiplostim in animals.

Wojciech Krzyzanski, Liviawati Sutjandra, Juan Jose Perez-Ruixo, Bethlyn Sloey, Andrew T Chow, Yow-Ming Wang

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 31 citations in OpenAlex.

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  13. A cell-level model of pharmacodynamics-mediated drug disposition.Journal of pharmacokinetics and pharmacodynamics · 2016
    Article
  14. Review
  15. Pharmacodynamic model for chemoradiotherapy-induced thrombocytopenia in mice.Journal of pharmacokinetics and pharmacodynamics · 2015
    Article
  16. Article
  17. Romiplostim dose-response in patients with myelodysplastic syndromes.British journal of clinical pharmacology · 2013
    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

6 authors at 3 institutions in 1 country.

Wojciech KrzyzanskiDepartment of Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
Liviawati Sutjandra
Juan Jose Perez-Ruixo
Bethlyn Sloey
Andrew T Chow
Yow-Ming Wang
Amgen (United States) · USUnited States Food and Drug Administration · USUniversity at Buffalo, State University of New York · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeRomiplostim is a novel thrombopoiesis-stimulating peptibody that targets the thrombopoietin c-Mpl receptor, resulting in increased platelet production. The pharmacodynamic-mediated disposition (PDMDD) and its stimulatory effect on platelet production in Sprague-Dawley rats, rhesus monkeys, and cynomolgus monkeys following IV bolus and SC administration at various dose levels were determined.

methodsThe pharmacokinetic (PK) profile was described by a PDMDD model that accounts for romiplostim binding to the c-Mpl receptor. The PD model contained a series of aging compartments for precursor cells in bone marrow and platelets. The stimulatory function was described by an on-and-off function operating on the fractional receptor occupancy (RO). The threshold effect, RO(thr), and K(D) parameters were determinants of drug potency, whereas S(max) reflected drug efficacy.

resultsThe model implicated that receptor-mediated clearance was negligible. RO(thr) estimated occupancies were 0.288, 0.385, 0.771 for rats, rhesus, and cynomolgus monkeys, respectively. The analogous estimated values of K(D) were 4.05, 2320, and 429 ng/mL, implying that romiplostim was much more potent in rats, which was confirmed by a dose-response (ratio of peak platelet count to baseline) relationship.

conclusionsThe model adequately described romiplostim serum concentrations and platelet counts in rats, rhesus monkeys, and cynomolgus monkeys, and quantified linear clearance, PDMDD, and potency of romiplostim.

Indexed as

AnimalsBlood PlateletsMacaca fascicularisMacaca mulattaModels, BiologicalPlatelet CountRatsRats, Sprague-DawleyReceptors, FcReceptors, ThrombopoietinRecombinant Fusion ProteinsThrombopoiesisThrombopoietinReceptors, FcReceptors, ThrombopoietinRecombinant Fusion ProteinsromiplostimThrombopoietin

Identifiers

PMID23250851
OpenAlexW2044643025

What OpenQuestion holds

Textmetadata
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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.