Evidence map›Paper›PMID 32603666›Full record

ArticleBiochemical pharmacology2020

Pharmacokinetics of gemcitabine and its amino acid ester prodrug following intravenous and oral administrations in mice.

Brian R Thompson, Jian Shi, Hao-Jie Zhu, David E Smith

Open access · greenAbstract read
In one paragraph

Article in Biochemical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Review
  3. Baicalin nano-micelles for dry eye disease: LC-MS/MS method validation, pharmacokinetics and pharmacodynamics in preclinical models.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Improved Antitumor Efficiency ofInternational journal of nanomedicine · 2024
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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 1 institution in 1 country.

Brian R ThompsonDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Jian ShiDepartment of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Hao-Jie ZhuDepartment of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
David E SmithDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: smithb@med.umich.edu.
University of Michigan–Ann Arbor · US

Funding

INTERDEPARTMENTAL TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007767 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ISOM, LORI L. · 1985 to 2019
$10.2M
Novel Transport and Activation Strategy to Improve the Bioavailability of Targeted ProdrugsR01GM115481 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AMIDON, GORDON L, SMITH, DAVID E · 2015 to 2018
$1.7M
NIGMS NIH HHS R01 GM115481NIGMS NIH HHS T32 GM007767
6 · The paper itself

Abstract

Gemcitabine is an intravenously administered anti-cancer nucleoside analogue. Systemic exposure following oral administration of gemcitabine is limited by extensive first-pass metabolism via cytidine deaminase (CDA) and potentially by saturation of nucleoside transporter-mediated intestinal uptake. An amino acid ester prodrug of gemcitabine, 5'-l-valyl-gemcitabine (V-Gem), was previously shown to be a substrate of the intestinally expressed peptide transporter 1 (PEPT1) and stable against CDA-mediated metabolism. However, preliminary studies did not evaluate the in vivo oral performance of V-Gem as compared to parent drug. In the present study, we evaluated the pharmacokinetics and in vivo oral absorption of gemcitabine and V-Gem following intravenous and oral administrations in mice. These studies revealed that V-Gem undergoes rapid systemic elimination (half-life < 1 min) and has a low oral bioavailability (<1%). Most importantly, the systemic exposure of gemcitabine was not different following oral administration of equimolar doses of gemcitabine (gemcitabine bioavailability of 18.3%) and V-Gem (gemcitabine bioavailability of 16.7%). Single-pass intestinal perfusions with portal blood sampling in mice revealed that V-Gem undergoes extensive activation in intestinal epithelial cells and that gemcitabine undergoes first-pass metabolism in intestinal epithelial cells. Thus, formulation of gemcitabine as the prodrug V-Gem does not increase systemic gemcitabine exposure following oral dosing, due, in part, to the instability of V-Gem in intestinal epithelial cells.

Indexed as

Administration, OralAmino AcidsAnimalsAntimetabolites, AntineoplasticBiological AvailabilityDeoxycytidineDrug StabilityEstersGemcitabineInjections, IntravenousJejunumMiceMice, Inbred C57BLMolecular StructureProdrugsAmino AcidsAntimetabolites, AntineoplasticDeoxycytidineEstersGemcitabineProdrugsBioavailabilityGemcitabinePEPT1Prodrug

Identifiers

PMID32603666
PMCPMC7606647
OpenAlexW3037479272

What OpenQuestion holds

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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.