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Cited by 47Drug Transport and Resistance MechanismsDrug Solubulity and Delivery SystemsPharmacogenetics and Drug Metabolism

The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.

Intestinal 5-Fluorouracil Absorption: Use of Ussing Chambers to Assess Transport and Metabolism

Smith, Philip, Mirabelli, Christopher, Fondacaro, Joseph, Ryan, Frederick, Dent, John·1988·Pharmaceutical Research
DOI 10.1023/a:1015950215230
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Abstract

We have employed an in vitro system to study transport and metabolism of organic molecules by gastrointestinal tissues. Such a system would aid in the evaluation of the potential for oral delivery of organic molecules. Transport and metabolism of 5-fluorouracil (5-FU) were studied using rabbit intestinal preparations. Unidirectional fluxes and metabolism were measured in vitro in Ussing chambers under short-circuit conditions. Results from these studies reveal that in ileum, proximal, and distal colon, steady-state fluxes of 5-FU (10 microM added to both bathing solutions) are established after 30 min and remain constant for at least 110 min. Transport of 5-FU under "sink" conditions with 10 microM 5-FU present in the mucosal or serosal bathing solution alone demonstrated similar rates of transport as under "nonsink" conditions. The concentration dependence of 5-FU fluxes indicates that the mucosal (m)-to-serosal (s) flux is composed of both a saturable and a linear component over the range of 1-100 microM in the ileum, whereas the s-to-m flux in the ileum and both fluxes in the colon are linear functions of concentration. Over the concentration range employed and the time course of these studies, 5-FU had no effect on the electrical properties of the ileum or colon. In the ileum, the m-to-s but not the s-to-m flux of 5-FU was reduced by (1) serosal ouabain (0.1 mM); (2) reduction of the bathing solution Na concentration; and (3) addition of uracil, thymine, thymidine, uridine, 2-deoxyuridine, or uridine-5'-monophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

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Crossref · 10.1023/a:1015950215230

Cites

18 of 18 references verified0 citation errors · 0 not checkable

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  • Ex vivo models such as everted sac or Ussing chamber have an expected lifespan (<8 hours) not sufficient to enable many studies on normal intestinal physiology, develop intestinal disease models, or study clinically relevant host-microbiome crosstalk.

    “Several ex vivo models, such as the everted sac18 or the Ussing chamber,19, 20 have been developed for drug transport assays; however, their expected lifespan (<8 hours) is not sufficient to enable many studies on normal intestinal physiology, develop intestinal disease models, or study clinically relevant host-microbiome crosstalk.”

    From Microfluidic Organ-on-a-Chip Models of Human Intestine (2018) · cites this paper as [20]

Citations

Cites

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Research works printed but not linked: 5

  1. J. L. Cohen, L. E. Irwin, G. J. Marshall, H. Darvey, and J. R. Bateman. Cancer Ther. Rep. 58:723–731 (1974).
  2. S. K. Sullivan and P. L. Smith. Am. J. Physiol. 251 (Gastrointest. Liver Physiol. 14):G436–G445 (1986).
  3. T. Z. Csaky. Fed. Proc. 22:3–7 (1963).
  4. B. C. Rudy and B. Z. Senkowski. In K. Florey (ed.), Analytical Profiles of Drug Substances, Academic Press, New York, 1973, pp. 221–244.
  5. J. B. Bateman, R. P. Pugh, F. R. Cassidy, G. J. Marshall, and L. E. Irwin. Cancer 28:907–913 (1971). · DOI

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Metadata

Authors
Smith, P., Mirabelli, C., Fondacaro, J., Ryan, F., & Dent, J.
ORCID
Smith, Philip
Venue
Pharmaceutical Research
Publisher
Springer Science and Business Media LLC
Published
1988-09
Volume
5
Issue
9
Pages
598-603
ISSN
  • 0724-8741 (ISSN-L)
  • 1573-904X
DOI
10.1023/a:1015950215230
OpenAlex
W158024441
Cited by
47
References
18
Citations by year
2025: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 1
FWCI
1.38
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pharmaceutical Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
5-fluorouracil, intestinal absorption, drug transport, drug metabolism, Ussing chamber, ileum, colon, sodium-dependent transport, competitive inhibition, unidirectional flux, oral drug delivery, rabbit intestine, short-circuit conditions, ouabain, sodium concentration, uridine 5'-monophosphate, thiopurines
MeSH terms
Animals, Chromatography, High Pressure Liquid, Colon, Fluorouracil, Ileum, Intestinal Absorption, Intestinal Mucosa, Rabbits, Sodium, In Vitro Techniques

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