ArticlePharmaceutical research2000
The influence of donor and reservoir additives on Caco-2 permeability and secretory transport of HIV protease inhibitors and other lipophilic compounds.
Article in Pharmaceutical research, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- Improving the Accuracy of Permeability Data to Gain Predictive Power: Assessing Sources of Variability in Assays Using Cell Monolayers.Membranes · 2024Review
- Prediction of Oral Drug Absorption in Rats from In Vitro Data.Pharmaceutical research · 2023Article
- Disease-drug and drug-drug interaction in COVID-19: Risk and assessment.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules.Pharmaceutics · 2021Article
- Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics.International journal of nanomedicine · 2021Review
- Using Human Plasma as an Assay Medium in Caco-2 Studies Improves Mass Balance for Lipophilic Compounds.Pharmaceutical research · 2018Article
- Prediction of the permeability of neutral drugs inferred from their solvation properties.Bioinformatics (Oxford, England) · 2016Article
- Application of Caco-2 cell line in herb-drug interaction studies: current approaches and challenges.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Review
- N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth.The American journal of pathology · 2013Article
- An integrated drug-likeness study for bicyclic privileged structures: from physicochemical properties to in vitro ADME properties.Molecular diversity · 2011Article
- Method to screen substrates of apical sodium-dependent bile acid transporter.The AAPS journal · 2008Article
- Effect of albumin on the biliary clearance of compounds in sandwich-cultured rat hepatocytes.Drug metabolism and disposition: the biological fate of chemicals · 2008Article
- Optimisation of the caco-2 permeability assay using experimental design methodology.Pharmaceutical research · 2008Article
- Predicting effect of food on extent of drug absorption based on physicochemical properties.Pharmaceutical research · 2007Article
- Transport of a novel anti-cancer agent, fenretinide across Caco-2 monolayers.Investigational new drugs · 2007Article
- Oral absorption of poorly water-soluble drugs: computer simulation of fraction absorbed in humans from a miniscale dissolution test.Pharmaceutical research · 2006Article
- Current industrial practices of assessing permeability and P-glycoprotein interaction.The AAPS journal · 2006Review
- Absorption rate limit considerations for oral phosphate prodrugs.Pharmaceutical research · 2003Article
- Transepithelial transport of prodrugs of the HIV protease inhibitors saquinavir, indinavir, and nelfinavir across Caco-2 cell monolayers.Pharmaceutical research · 2002Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo optimize the conditions for determining Caco-2 permeation of HIV protease inhibitors and other lipophilic compounds, and to compare cyclic urea HIV protease inhibitors with marketed compounds.
methodsAbsorptive and secretory Caco-2 membrane permeation studies were performed with HIV protease inhibitors and various reference compounds, examining the effects of adding the solubilizing agents dimethylacetamide (DMAC) and albumin in donor and reservoir compartments, respectively.
resultsDMAC was useful as an additive in the donor vehicles, increasing the dissolved concentrations of poorly water-soluble HIV protease inhibitors, and enabling more reliable determination of P(app) values. Donor vehicles containing up to 5% DMAC could be used without altering Caco-2 barrier function, as indicated by the lack of effect on permeabilities of reference compounds with diverse absorption characteristics. The utilization of a reservoir containing albumin resulted in marked increases in absorptive Papp values for some HIV protease inhibitors as well as other lipophilic, highly protein bound compounds, consistent with albumin increasing the release of these compounds from the cell monolayer.
conclusionsPoorly soluble, lipophilic, highly bound compounds may require using solubilizing agents in the donor and reservoir compartments of Caco-2 permeation experiments for estimating in vivo absorption potential. If the reservoir does not provide adequate sink conditions, cellular retention could over-emphasize the contributions of secretory transport. The cyclic ureas, DMP 450, DMP 850, and DMP 851, have Caco-2 permeabilities suggestive of moderate-to-high oral absorption potential in humans.
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