| 1. |
- Matsson, Pär, et al.
(författare)
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A Tribute to Professor Per Artursson - Scientist, Explorer, Mentor, Innovator, and Giant in Pharmaceutical Research
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 2-11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This issue of the Journal of Pharmaceutical Sciences is dedicated to Professor Per Artursson and the groundbreaking contributions he has made and continues to make in the Pharmaceutical Sciences. Per is one of the most cited researchers in his field, with more than 30,000 citations and an h-index of 95 as of September 2020. Importantly, these citations are distributed over the numerous fields he has explored, clearly showing the high impact the research has had on the discipline. We provide a short portrait of Per, with emphasis on his personality, driving forces and the inspirational sources that shaped his career as a world-leading scientist in the field. He is a curious scientist who deftly moves between disciplines and has continued to innovate, expand boundaries, and profoundly impact the pharmaceutical sciences throughout his career. He has developed new tools and provided insights that have significantly contributed to today’s molecular and mechanistic approaches to research in the fields of intestinal absorption, cellular disposition, and exposure-efficacy relationships of pharmaceutical drugs. We want to celebrate these important contributions in this special issue of the Journal of Pharmaceutical Sciences in Per’s honor.
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| 2. |
- Artursson, Per, et al.
(författare)
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Caco-2 monolayers in experimental and theoretical predictions of drug transport
- 2012
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Ingår i: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 64:S, s. 280-289
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Forskningsöversikt (refereegranskat)abstract
- This review examines the use of Caco-2 monolayers in the prediction of intestinal drug absorption. First, the different routes of drug transport in Caco-2 monolayers are compared with those seen in vivo. Second, the prediction of drug absorption in vivo from transport experiments in cell monolayers is discussed for different classes of drugs. Finally, the use of Caco-2 monolayers as a reference model in physico-chemical and theoretical predictions of drug absorption is discussed. We conclude that Caco-2 monolayers can be used to identify drugs with potential absorption problems, and possibly also to select drugs with optimal passive absorption characteristics from series of pharmacologically active molecules generated in drug discovery programs.
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| 3. |
- Gennemark, Peter, et al.
(författare)
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An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
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| 4. |
- John, Sternbeck, et al.
(författare)
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Organiska miljögifter i fisk från svenska bakgrundsområden
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fisk från nio svenska lokaler, representerande sötvatten, kust och utsjö, har analyserats på PBDE (polybromerade difenyletrar), HBCD, PAH (polycykliska aromatiska kolväten), Klorerade bensener, PCB, ftalater, och klorerade dioxiner och furander i fiskmuskel. Dessutom har pentaklorfenol, triclosan och tetrabrombisfenol A analyserats i fiskgalla från tre av dessa lokaler.
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| 5. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Palm, Katrin
(författare)
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Experimental and theoretical predictions of intestinal drug absorption
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The subject of this thesis is the development of better experimental and computational predictions of the intestinal absorption properties of new drug candidates. In the last decade the drug discovery process has produced an increasing number of new drug candidates by the use of high throughput screening techniques. As a result, there is a demand for better screening methods also for biopharmaceutical properties such as oral drug absorption.The main objective was to develop computational methods to predict passive intestinal epithelial permeability from structural descriptors that take the three-dimensional shape of the molecules into consideration. Many molecular characteristics are influenced by conformational properties and intramolecular interactions. Few computational methods, however, take these factors adequately into consideration. Properties of the molecular surface are of special interest since the surface area is influenced by the three-dimensional shape of the molecule, and will determine how the compound is perceived by its surroundings.Initially, monolayers of human intestinal epithelial Caco-2 cells were confirmed to be a good in vitro model of the human intestinal epithelium in vivo for studies of passive transcellular drug transport. Thus, Caco-2 cell monolayers were concluded to be suitable for studies of relationships between the molecular structure of drugs and their ability to permeate the intestinal epithelium.A computational method based on the calculation of dynamic polar molecular surface area (PSAd) was developed for the prediction of intestinal epithelial drug absorption. The PSAd takes into consideration the three-dimensional shape and flexibility of the molecules. PSAd was found to better predict the intestinal epithelial permeability to drugs than more established computed predictors, e.g. the octanol/water partition coefficient and hydrogen bond-number, as well as newer experimental screening methods such as immobilised liposome chromatography. These results indicate that the hydrogen-bonding related descriptor PSAd is a promising new predictor of epithelial permeability.Although additional molecular properties, such as molecular charge, need to be included in a generally applicable method, PSAd or hydrogen bonding potential seems to be the dominating molecular property that determines the epithelial drug transport.
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| 7. |
- Sternbeck, John, et al.
(författare)
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Organiska miljögifter i fisk från svenska bakgrundslokaler
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fisk från nio svenska lokaler, representerande sötvatten, kust och utsjö, har analyserats på PBDE (polybromerade difenyletrar), HBCD, PAH (polycykliska aromatiska kolväten), klorerade bensener, PCB, ftalater, och klorerade dioxiner och furaner i fiskmuskel. Dessutom har pentaklorfenol, triclosan och tetrabrombisfenol A analyserats i fiskgalla från tre av dessa lokaler.
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