{"entity": "journal", "iuid": "4f91d8069ee04825b559b61e55d1db93", "timestamp": "2026-06-08T12:04:24.724Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/journal/J%20Pharm%20Sci.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/journal/J%20Pharm%20Sci"}}, "title": "J Pharm Sci", "issn": "1520-6017", "issn-l": "0022-3549", "publications_count": 6, "publications": [{"entity": "publication", "iuid": "5b079a48d74140b5b245c67f83614c2d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5b079a48d74140b5b245c67f83614c2d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5b079a48d74140b5b245c67f83614c2d"}}, "title": "Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease.", "authors": [{"family": "Asad", "given": "Shno", "initials": "S"}, {"family": "Wegler", "given": "Christine", "initials": "C"}, {"family": "Ahl", "given": "David", "initials": "D"}, {"family": "Bergstr\u00f6m", "given": "Christel A S", "initials": "CAS"}, {"family": "Phillipson", "given": "Mia", "initials": "M"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Teleki", "given": "Alexandra", "initials": "A"}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "J Pharm Sci", "issn": "1520-6017", "issn-l": "0022-3549", "volume": "110", "issue": "1", "pages": "239-250"}, "abstract": "Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for non-invasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal- and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.", "doi": "10.1016/j.xphs.2020.11.001", "pmid": "33159915", "labels": {"Alexandra Teleki": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "S0022-3549(20)30685-7"}], "notes": [], "created": "2020-11-30T21:38:59.620Z", "modified": "2022-11-04T11:32:13.830Z"}, {"entity": "publication", "iuid": "895a9bb0237543e392abe5455e9d6863", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/895a9bb0237543e392abe5455e9d6863.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/895a9bb0237543e392abe5455e9d6863"}}, "title": "A CRISPR-Cas9 Generated MDCK Cell Line Expressing Human MDR1 Without Endogenous Canine MDR1 (cABCB1): An Improved Tool for Drug Efflux Studies.", "authors": [{"family": "Karlgren", "given": "Maria", "initials": "M"}, {"family": "Simoff", "given": "Ivailo", "initials": "I"}, {"family": "Backlund", "given": "Maria", "initials": "M"}, {"family": "Wegler", "given": "Christine", "initials": "C"}, {"family": "Keiser", "given": "Markus", "initials": "M"}, {"family": "Handin", "given": "Niklas", "initials": "N"}, {"family": "M\u00fcller", "given": "Janett", "initials": "J"}, {"family": "Lundquist", "given": "Patrik", "initials": "P"}, {"family": "Jareborg", "given": "Anne-Christine", "initials": "AC"}, {"family": "Oswald", "given": "Stefan", "initials": "S"}, {"family": "Artursson", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2017-09-00", "journal": {"title": "J Pharm Sci", "issn": "1520-6017", "volume": "106", "issue": "9", "pages": "2909-2913", "issn-l": "0022-3549"}, "abstract": "Madin-Darby canine kidney (MDCK) II cells stably transfected with transport proteins are commonly used models for drug transport studies. However, endogenous expression of especially canine MDR1 (cMDR1) confounds the interpretation of such studies. Here we have established an MDCK cell line stably overexpressing the human MDR1 transporter (hMDR1; P-glycoprotein), and used CRISPR-Cas9 gene editing to knockout the endogenous cMDR1. Genomic screening revealed the generation of a clonal cell line homozygous for a 4-nucleotide deletion in the canine ABCB1 gene leading to a frameshift and a premature stop codon. Knockout of cMDR1 expression was verified by quantitative protein analysis and functional studies showing retained activity of the human MDR1 transporter. Application of this cell line allowed unbiased reclassification of drugs previously defined as both substrates and non-substrates in different studies using commonly used MDCK-MDR1 clones. Our new MDCK-hMDR1 cell line, together with a previously developed control cell line, both with identical deletions in the canine ABCB1 gene and lack of cMDR1 expression represent excellent in\u00a0vitro tools for use in drug discovery.", "doi": "10.1016/j.xphs.2017.04.018", "pmid": "28450237", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0022-3549(17)30251-4"}], "notes": [], "created": "2018-12-05T11:56:00.872Z", "modified": "2018-12-05T11:56:00.890Z"}, {"entity": "publication", "iuid": "91bd83614eac463fae3a7053e89fb5bd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/91bd83614eac463fae3a7053e89fb5bd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/91bd83614eac463fae3a7053e89fb5bd"}}, "title": "The Impact of Liposomal Formulations on the Release and Brain Delivery of Methotrexate: An In\u00a0Vivo Microdialysis Study.", "authors": [{"family": "Hu", "given": "Yang", "initials": "Y"}, {"family": "Rip", "given": "Jaap", "initials": "J"}, {"family": "Gaillard", "given": "Pieter J", "initials": "PJ"}, {"family": "de Lange", "given": "Elizabeth C M", "initials": "ECM"}, {"family": "Hammarlund-Udenaes", "given": "Margareta", "initials": "M"}], "type": "journal article", "published": "2017-09-00", "journal": {"title": "J Pharm Sci", "issn": "1520-6017", "volume": "106", "issue": "9", "pages": "2606-2613", "issn-l": "0022-3549"}, "abstract": "The impact of liposomal formulations on the in\u00a0vivo release and brain delivery of methotrexate (MTX) was quantitatively assessed in rats. Two PEGylated liposomal MTX formulations based on hydrogenated soy phosphatidylcholine (HSPC) or egg-yolk phosphatidylcholine (EYPC) were prepared. The drug release and uptake into the brain after intravenous administration of both formulations were compared with unformulated MTX by determining the released, unbound MTX in brain and plasma using microdialysis. Total MTX concentrations in plasma were determined using regular blood sampling. The administration of both high- and low-dose EYPC liposomes resulted in 10 times higher extent of MTX release in plasma compared to that obtained from HSPC liposomes (p < 0.05). MTX itself possessed limited brain uptake with steady-state unbound brain-to-plasma concentration ratio (K", "doi": "10.1016/j.xphs.2017.03.009", "pmid": "28322936", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0022-3549(17)30166-1"}], "notes": [], "created": "2018-12-05T12:25:39.815Z", "modified": "2018-12-05T12:25:39.834Z"}, {"entity": "publication", "iuid": "d67da888e2ee4b8593de187e22c6aaf3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d67da888e2ee4b8593de187e22c6aaf3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d67da888e2ee4b8593de187e22c6aaf3"}}, "title": "The Proteome of Filter-Grown Caco-2 Cells With a Focus on Proteins Involved in Drug Disposition.", "authors": [{"family": "\u00d6lander", "given": "Magnus", "initials": "M"}, {"family": "Wi\u015bniewski", "given": "Jacek R", "initials": "JR"}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Lundquist", "given": "Patrik", "initials": "P"}, {"family": "Artursson", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2016-02-00", "journal": {"title": "J Pharm Sci", "issn": "1520-6017", "volume": "105", "issue": "2", "pages": "817-827", "issn-l": "0022-3549"}, "abstract": "Caco-2 cells are widely used in studies of intestinal cell physiology and drug transport. Here, the global proteome of filter-grown Caco-2 cells was quantified using the total protein approach and compared with the human colon and jejunum proteomes. In total, 8096 proteins were identified. In-depth analysis of proteins defining enterocyte differentiation-including brush-border hydrolases, integrins, and adherens and tight junctions-gave near-complete coverage of the expected proteins. Three hundred twenty-seven absorption, distribution, metabolism and excretion proteins were identified, including 112 solute carriers and 20 ATP-binding cassette transporters. OATP2B1 levels were 16-fold higher in Caco-2 cells than in jejunum. To investigate the impact of this difference on in vitro-in vivo extrapolations, we studied the uptake kinetics of the OATP2B1 substrate pitavastatin in Caco-2 monolayers, and found that the contribution of OATP2B1 was 60%-70% at clinically relevant intestinal concentrations. Pitavastatin kinetics was combined with transporter concentrations to model the contribution of active transport and membrane permeation in the jejunum. The lower OATP2B1 expression in jejunum led to a considerably lower transporter contribution (<5%), suggesting that transmembrane diffusion dominates pitavastatin absorption in vivo. In conclusion, we present the first in-depth quantification of the filter-grown Caco-2 proteome. We also demonstrate the crucial importance of considering transporter expression levels for correct interpretation of drug transport routes across the human intestine.", "doi": "10.1016/j.xphs.2015.10.030", "pmid": "26869432", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0022-3549(15)00031-3"}], "notes": [], "created": "2018-12-05T09:57:33.676Z", "modified": "2018-12-05T09:57:33.695Z"}, {"entity": "publication", "iuid": "2d01bada082f4e338e9c9e1b82737339", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2d01bada082f4e338e9c9e1b82737339.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2d01bada082f4e338e9c9e1b82737339"}}, "title": "Oxymorphone active uptake at the blood-brain barrier and population modeling of its pharmacokinetic-pharmacodynamic relationship.", "authors": [{"family": "Sadiq", "given": "Muhammad Waqas", "initials": "MW"}, {"family": "Bostr\u00f6m", "given": "Emma", "initials": "E"}, {"family": "Keizer", "given": "Ron", "initials": "R"}, {"family": "Bj\u00f6rkman", "given": "Sven", "initials": "S"}, {"family": "Hammarlund-Udenaes", "given": "Margareta", "initials": "M"}], "type": "journal article", "published": "2013-09-00", "journal": {"title": "J Pharm Sci", "issn": "1520-6017", "volume": "102", "issue": "9", "pages": "3320-3331", "issn-l": "0022-3549"}, "abstract": "The aim of this study was to characterize the blood-brain barrier (BBB) transport and pharmacokinetics-pharmacodynamics (PKPD) relationship of oxymorphone and to further elucidate its possible contribution to oxycodone analgesia. The BBB transport of oxymorphone was studied using microdialysis in male Sprague-Dawley rats. Samples from microdialysis blood and brain probes, brain tissue, and plasma were analyzed by liquid chromatography with tandem mass spectrometry. The effect was measured as tail-flick latency. The study consisted of a PKPD experiment with combined microdialysis and antinociceptive measurements (n = 8), and another antinociceptive effect experiment (n = 9) using a 10 times lower dose. The combined data were analyzed with an integrated PKPD model in nonlinear mixed effect modeling utilizing a specific method (M3) for handling missing PD observations. The concentration of unbound oxymorphone was higher in brain than in blood, with a ratio of 1.9 (RSE, 9.7%), indicating active uptake at the BBB. The integrated PKPD model described the oxymorphone BBB transport and PKPD relationship successfully, with an EC50 in the brain of 63 ng/mL, and the M3 method was able to address the issue of censored observations. Oxymorphone has active uptake transport at the BBB in rats, with moderate uptake clearance to the brain. Its contribution to analgesia after oxycodone administration is not significant.", "doi": "10.1002/jps.23492", "pmid": "23463542", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0022-3549(15)30915-1"}], "notes": [], "created": "2018-12-05T11:14:21.926Z", "modified": "2018-12-05T11:14:21.945Z"}, {"entity": "publication", "iuid": "994f37819c8b47fba0698b68657a6cdb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/994f37819c8b47fba0698b68657a6cdb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/994f37819c8b47fba0698b68657a6cdb"}}, "title": "Impact of CYP3A5*3 and CYP2C8-HapC on paclitaxel/carboplatin-induced myelosuppression in patients with ovarian cancer.", "authors": [{"family": "Gr\u00e9en", "given": "Henrik", "initials": "H"}, {"family": "Khan", "given": "Muhammad Suleman", "initials": "MS"}, {"family": "Jakobsen-Falk", "given": "Ingrid", "initials": "I"}, {"family": "\u00c5vall-Lundqvist", "given": "Elisabeth", "initials": "E"}, {"family": "Peterson", "given": "Curt", "initials": "C"}], "type": "journal article", "published": "2011-10-00", "journal": {"title": "J Pharm Sci", "issn": "1520-6017", "volume": "100", "issue": "10", "pages": "4205-4209", "issn-l": "0022-3549"}, "abstract": "The influence of genetic variants on paclitaxel-induced toxicity is of considerable interest for reducing adverse drug reactions. Recently, the genetic variants CYP2C8*3, CYP2C8-HapC, and CYP3A5*3 were associated with paclitaxel-induced neurotoxicity. We, therefore, investigated the impact of CYP2C8-HapC and CYP3A5*3 on paclitaxel/carboplatin-induced myelosuppression and neurotoxicity. Thirty-three patients from a prospective pharmacokinetics study were genotyped using pyrosequencing. Patients with variant alleles of CYP2C8-HapC were found to have significantly lower nadir values of both leukocytes and neutrophils (p < 0.05) than patients with the wild-type genotype. CYP3A5*3/*1 patients were shown to have borderline, significantly lower nadir values of leukocytes (p = 0.07) than *3/*3 patients. Combining the two genotypes resulted in a significant correlation with both leukopenia and neutropenia (p = 0.01). No effect of these genetic variants on neurotoxicity could be shown in this rather small study, but their importance for paclitaxel-induced toxicity could be confirmed.", "doi": "10.1002/jps.22680", "pmid": "21702053", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S0022-3549(15)31926-2"}], "notes": [], "created": "2018-12-05T09:44:03.501Z", "modified": "2018-12-05T09:44:03.535Z"}], "created": "2018-12-05T09:44:03.516Z", "modified": "2020-11-27T13:12:54.715Z"}