No Evidence for the Involvement of the Multidrug Resistance-Associated Protein and/or the Monocarboxylic Acid Transporter in the Intestinal Transport of Fluvastatin in the Rat.
Abstract
Fluvastatin, an amphiphilic anion, shows a nonlinear increase in effective intestinal permeability (P(eff)) with increasing lumenal concentrations in rats. The main objective of this study was to investigate whether or not this observation could be attributed to an efflux-mediated transport by the multidrug resistance-associated protein (MRP). In parallel, we investigated the possible involvement of the monocarboxylic acid transporter (MCT) in the rapid intestinal absorption of fluvastatin. Single-pass perfusions were performed in the ileum and colon of the rat, with and without the presence of well-established inhibitors/substrates for the MRP (probenecid) and the MCT (nicotinic acid). The results suggest that neither the MRP nor the MCT are involved to any significant extent in the absorption process of fluvastatin in the rat intestine. Thus, the previously reported concentration-dependent P(eff) of fluvastatin in these intestinal regions of the rat is probably not attributable to saturation of any efflux mediated by MRP.
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FS uptake into cells is dependent on pH.
“FS uptake into cells is dependent on pH.”
From Inhibition of<i>Candida albicans</i>by Fluvastatin Is Dependent on pH (2009) · cites this paper as [4]
The low-dose growth-inhibitory action of FS at low pH can be understood by the previously demonstrated pH dependency of FS uptake across biological membranes.
“The low-dose growth-inhibitory action of FS at low pH values can be understood in light of the previously demonstrated pH dependency of FS uptake across biological membranes [4].”
From Inhibition of<i>Candida albicans</i>by Fluvastatin Is Dependent on pH (2009) · cites this paper as [4]
The uncharged protonated form of FS is taken up more readily than the charged molecule at serum pH.
“The uncharged protonated form of FS in the acidic pH of the intestine is taken up more readily that the charged molecule is present at serum pH [4].”
From Inhibition of<i>Candida albicans</i>by Fluvastatin Is Dependent on pH (2009) · cites this paper as [4]
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Inhibition of<i>Candida albicans</i>by Fluvastatin Is Dependent on pH
Schmidt, M., Dzogbeta, S., & Boyer, M. P. (2009) · Research Letters in Biochemistry · doi:10.1155/2009/151424 · Cited by 7 · see citing works
- Authors
- Lindahl, A., Frid, S., Ungell, A., & Lennernas, H.
- Affiliations
- Uppsala University (SE)
- ORCID
- Lindahl, A
- Venue
- AAPS PharmSci
- Published
- 2000
- Volume
- 02
- Issue
- 03
- Pages
- e26
- ISSN
- 1522-1059 (ISSN-L)
- OpenAlex
- W4205829098
- Cited by
- 19
- References
- 26
- Citations by year
- 2024: 1 · 2023: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- AAPS PharmSci (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
- fluvastatin, multidrug resistance-associated protein, monocarboxylate transporters, intestinal absorption, intestinal permeability, efflux transport, probenecid, nicotinic acid, single-pass perfusion, rat intestine, statins
- MeSH terms
- Fluvastatin, Multidrug Resistance-Associated Protein 2, Acyl Coenzyme A, Animals, Colon, Enzyme Inhibitors, Fatty Acids, Monounsaturated, Ileum, Indoles, Intestinal Absorption, Intestinal Mucosa, Male, Niacin, Probenecid, Rats, Sprague-Dawley, Membrane Transport Proteins, ATP-Binding Cassette, Sub-Family C Proteins, Monocarboxylic Acid Transporters, Rats
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