{"entity": "researcher", "timestamp": "2026-08-22T06:56:28.288Z", "family": "Wegler", "given": "Christine", "initials": "C", "orcid": "0000-0002-2810-7518", "affiliations": ["Department of Pharmacy, Uppsala University, 752 37 Uppsala, Sweden.", "DMPK, Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, 431 50 Gothenburg, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10"}}, "publications": [{"entity": "publication", "iuid": "efabd2364eb647cebc5a8550720e040b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/efabd2364eb647cebc5a8550720e040b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/efabd2364eb647cebc5a8550720e040b"}}, "title": "Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity.", "authors": [{"family": "Kvitne", "given": "Kine Eide", "initials": "KE", "orcid": "0000-0001-8118-7660", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cc96a6df2d34cf7a41eb1fd7ba2887e.json"}}, {"family": "Krogstad", "given": "Veronica", "initials": "V"}, {"family": "Wegler", "given": "Christine", "initials": "C", "orcid": "0000-0002-2810-7518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10.json"}}, {"family": "Johnson", "given": "Line Kristin", "initials": "LK"}, {"family": "Kringen", "given": "Marianne K", "initials": "MK"}, {"family": "Hovd", "given": "Markus Herberg", "initials": "MH", "orcid": "0000-0002-6077-0934", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/40bec1eda0684e43a25fb3a9552d9f03.json"}}, {"family": "Hertel", "given": "Jens K", "initials": "JK"}, {"family": "Heijer", "given": "Maria", "initials": "M"}, {"family": "Sandbu", "given": "Rune", "initials": "R"}, {"family": "Skovlund", "given": "Eva", "initials": "E"}, {"family": "Artursson", "given": "Per", "initials": "P"}, {"family": "Karlsson", "given": "Cecilia", "initials": "C"}, {"family": "Andersson", "given": "Shalini", "initials": "S"}, {"family": "Andersson", "given": "Tommy B", "initials": "TB"}, {"family": "Hjelmesaeth", "given": "J\u00f8ran", "initials": "J"}, {"family": "\u00c5sberg", "given": "Anders", "initials": "A", "orcid": "0000-0002-0628-1769", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/153c90f914b4461b8fa381a2e24a7954.json"}}, {"family": "Jansson-L\u00f6fmark", "given": "Rasmus", "initials": "R"}, {"family": "Christensen", "given": "Hege", "initials": "H"}, {"family": "Robertsen", "given": "Ida", "initials": "I", "orcid": "0000-0001-9401-7716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fbbacb93696b4b42b4796fc8a3dab7b2.json"}}], "type": "clinical trial", "published": "2022-09-00", "journal": {"title": "Br J Clin Pharmacol", "issn": "1365-2125", "volume": "88", "issue": "9", "pages": "4121-4133", "issn-l": null}, "abstract": "Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls.\n\nThis trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations.\n\nMean \u00b1 SD weight loss from baseline was similar in the RYGB-group (13 \u00b1 2.4%) and the diet group (10.5 \u00b1 3.9%) at week 9, but differed at year 2 (RYGB -30 \u00b1 6.9%, diet -3.1 \u00b1 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference -0.30 [-0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities.\n\nOur findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.", "doi": "10.1111/bcp.15349", "pmid": "35404513", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9541356"}], "notes": [], "created": "2026-08-21T12:17:28.245Z", "modified": "2026-08-21T12:17:28.434Z"}, {"entity": "publication", "iuid": "77e1d906fe0d4fc4a4519f8d9f6a303b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/77e1d906fe0d4fc4a4519f8d9f6a303b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/77e1d906fe0d4fc4a4519f8d9f6a303b"}}, "title": "Influence of Proteome Profiles and Intracellular Drug Exposure on Differences in CYP Activity in Donor-Matched Human Liver Microsomes and Hepatocytes.", "authors": [{"family": "Wegler", "given": "Christine", "initials": "C", "orcid": "0000-0002-2810-7518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10.json"}}, {"family": "Matsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-9094-2581", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57286366d8624b689b3809ede3cab002.json"}}, {"family": "Krogstad", "given": "Veronica", "initials": "V"}, {"family": "Urdzik", "given": "Jozef", "initials": "J"}, {"family": "Christensen", "given": "Hege", "initials": "H"}, {"family": "Andersson", "given": "Tommy B", "initials": "TB"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9908209a413a4088b6bf44a924d27319.json"}}], "type": "journal article", "published": "2021-04-05", "journal": {"title": "Mol. Pharm.", "issn": "1543-8392", "volume": "18", "issue": "4", "pages": "1792-1805", "issn-l": "1543-8384"}, "abstract": "Human liver microsomes (HLM) and human hepatocytes (HH) are important in vitro systems for studies of intrinsic drug clearance (CLint) in the liver. However, the CLint values are often in disagreement for these two systems. Here, we investigated these differences in a side-by-side comparison of drug metabolism in HLM and HH prepared from 15 matched donors. Protein expression and intracellular unbound drug concentration (Kpuu) effects on the CLint were investigated for five prototypical probe substrates (bupropion-CYP2B6, diclofenac-CYP2C9, omeprazole-CYP2C19, bufuralol-CYP2D6, and midazolam-CYP3A4). The samples were donor-matched to compensate for inter-individual variability but still showed systematic differences in CLint. Global proteomics analysis outlined differences in HLM from HH and homogenates of human liver (HL), indicating variable enrichment of ER-localized cytochrome P450 (CYP) enzymes in the HLM preparation. This suggests that the HLM may not equally and accurately capture metabolic capacity for all CYPs. Scaling CLint with CYP amounts and Kpuu could only partly explain the discordance in absolute values of CLint for the five substrates. Nevertheless, scaling with CYP amounts improved the agreement in rank order for the majority of the substrates. Other factors, such as contribution of additional enzymes and variability in the proportions of active and inactive CYP enzymes in HLM and HH, may have to be considered to avoid the use of empirical scaling factors for prediction of drug metabolism.", "doi": "10.1021/acs.molpharmaceut.1c00053", "pmid": "33739838", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8041379"}], "notes": [], "created": "2026-08-20T08:12:29.330Z", "modified": "2026-08-20T08:12:29.465Z"}, {"entity": "publication", "iuid": "1481ce8eac564e40928016c3bbb9c2bc", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1481ce8eac564e40928016c3bbb9c2bc.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1481ce8eac564e40928016c3bbb9c2bc"}}, "title": "Multiple-Enzyme-Digestion Strategy Improves Accuracy and Sensitivity of Label- and Standard-Free Absolute Quantification to a Level That Is Achievable by Analysis with Stable Isotope-Labeled Standard Spiking.", "authors": [{"family": "Wi\u015bniewski", "given": "Jacek R", "initials": "JR", "orcid": "0000-0002-8452-5095", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/873ef644d5314caab5856b80b9acb222.json"}}, {"family": "Wegler", "given": "Christine", "initials": "C", "orcid": "0000-0002-2810-7518", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fcb45d19c52847f19bd5c0aa296afe10.json"}}, {"family": "Artursson", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2019-01-04", "journal": {"title": "J. Proteome Res.", "issn": "1535-3907", "volume": "18", "issue": "1", "pages": "217-224", "issn-l": "1535-3893"}, "abstract": "Quantification of individual proteins is an essential task in understanding biological processes. For example, determination of concentrations of proteins transporting and metabolizing xenobiotics is a prerequisite for drug disposition predictions in humans based on in vitro data. So far, this task has frequently been accomplished by targeted proteomics. This type of analyses requires preparation of stable isotope labeled standards for each protein of interest. The selection of appropriate standard peptides is usually tedious and the number of proteins that can be studied in a single experiment by these approaches is limited. In addition, incomplete digestion of proteins often affects the accuracy of the quantification. To circumvent these constrains in proteomic protein quantification, label- and standard-free approaches, such as \"total protein approach\" (TPA) have been proposed. Here we directly compare an approach using stable isotope labeled (SIL) standards and TPA for quantification of transporters and enzymes in human liver samples within the same LC-MS/MS runs. We show that TPA is a convenient alternative to SIL-based methods. Optimization of the sample preparation beyond commonly used single tryptic digestion, by adding consecutive cleavage steps, improves accuracy and reproducibility of the TPA method to a level, which is achievable by analysis using stable isotope-labeled standard spiking.", "doi": "10.1021/acs.jproteome.8b00549", "pmid": "30336047", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-21T11:34:11.621Z", "modified": "2026-08-21T11:34:11.732Z"}]}