ArticlePharmaceutical research2002
Transepithelial transport of prodrugs of the HIV protease inhibitors saquinavir, indinavir, and nelfinavir across Caco-2 cell monolayers.
Article in Pharmaceutical research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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.
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Who cites it
9 citing papers in PubMed, 33 citations in OpenAlex.
- Glutamine transporters as pharmacological targets: From function to drug design.Asian journal of pharmaceutical sciences · 2020Review
- Evaluation of Marine Diindolinonepyrane in Vitro and in Vivo: Permeability Characterization in Caco-2 Cells Monolayer and Pharmacokinetic Properties in Beagle Dogs.Marine drugs · 2019Article
- Biocompatibility Profile and In Vitro Cellular Uptake of Self-assembled Alginate Nanoparticles.Molecules (Basel, Switzerland) · 2019Article
- Review
- Targeting SVCT for enhanced drug absorption: synthesis and in vitro evaluation of a novel vitamin C conjugated prodrug of saquinavir.International journal of pharmaceutics · 2011Article
- Montelukast is a potent and durable inhibitor of multidrug resistance protein 2-mediated efflux of taxol and saquinavir.Biological & pharmaceutical bulletin · 2009Article
- FK506-binding protein (FKBP) partitions a modified HIV protease inhibitor into blood cells and prolongs its lifetime in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats.International journal of pharmaceutics · 2007Article
- Functional characterization of peptide transporters in MDCKII-MDR1 cell line as a model for oral absorption studies.International journal of pharmaceutics · 2007Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose[corrected] This study is dedicated to the permeation of various amino acid-, D-glucose-, and PEG-conjugates of indinavir, saquinavir, and nelfinavir across monolayers of Caco-2 cells as models of the intestinal barrier. This screening is aimed at detecting the most promising prodrugs for improving the intestinal absorption of these protease inhibitors.
methodsThe bidirectional transport of the prodrugs was investigated using P-gp-expressing Caco-2 monolayers grown on membrane inserts using high-performance liquid chromatography for quantitation.
resultsThe L-valyl, L-leucyl, and L-phenylalanyl ester conjugates led to an enhancement of the absorptive flux of indinavir or saquinavir. These results are likely attributable to an active transport mechanism and/or to a decrease of their efflux by carriers such as P-gp. Connection of tyrosine through its hydroxyl, of D-glucose, or of polyethylene glycol decreased their absorptive and secretory diffusion.
conclusionsConjugation of the protease inhibitors to amino acids constitutes a most appealing alternative that could improve their intestinal absorption and oral bioavailability. Whether it could improve their delivery into the central nervous system remains to be explored. D-Glucose conjugation will most probably not improve their intestinal absorption or their crossing of the blood-brain barrier. If some pharmacologic benefits are to be expected from PEG-protease inhibitor conjugates, they must then be administered intravenously.
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Registered trials
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.