Plasma concentrations of active simvastatin acid are increased by gemfibrozil
Abstract
BACKGROUND: Concomitant treatment with simvastatin and gemfibrozil, two lipid-lowering drugs, has been associated with occurrence of myopathy in case reports. The aim of this study was to determine whether gemfibrozil affects the pharmacokinetics of simvastatin and whether it affects CYP3A4 activity in vitro. METHODS: A double-blind, randomized crossover study with two phases (placebo and gemfibrozil) was carried out. Ten healthy volunteers were given gemfibrozil (600 mg twice daily) or placebo orally for 3 days. On day 3 they ingested a single 40-mg dose of simvastatin. Plasma concentrations of simvastatin and simvastatin acid were measured up to 12 hours. In addition, the effect of gemfibrozil (0 to 1,200 micromol/L) on midazolam 1'-hydroxylation, a CYP3A4 model reaction, was investigated in human liver microsomes in vitro. RESULTS: Gemfibrozil increased the mean total area under the plasma concentration-time curve of simvastatin [AUC(0-infinity)] by 35% (P < .01) and the AUC(0-infinity) of simvastatin acid by 185% (P < .001). The elimination half-life of simvastatin was increased by 74% (P < .05), and that of simvastatin acid was increased by 51% (P < .01) by gemfibrozil. The peak concentration of simvastatin acid was increased by 112%, from 3.20 +/- 2.73 ng/mL to 6.78 +/- 4.67 ng/mL (mean +/- SD; P < .01). In vitro, gemfibrozil showed no inhibition of midazolam 1'-hydroxylation. CONCLUSIONS: Gemfibrozil increases plasma concentrations of simvastatin and, in particular, its active form, simvastatin acid, suggesting that the increased risk of myopathy in combination treatment is, at least partially, of a pharmacokinetic origin. Because gemfibrozil does not inhibit CYP3A4 in vitro, the mechanism of the pharmacokinetic interaction is probably inhibition of non-CYP3A4-mediated metabolism of simvastatin acid.
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There are DDI and DGI studies demonstrating SVA influx to hepatocytes via the membrane transporter OATP1B1.
“Additionally, there are DDI and drug–gene interaction (DGI) studies demonstrating SVA influx to hepatocytes via the membrane transporter OATP1B1. 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35”
From Does the choice of applied physiologically‐based pharmacokinetics platform matter? A case study on simvastatin disposition and drug–drug interaction (2022) · cites this paper as [28]
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Graham, D. J. (2004) · JAMA · doi:10.1001/jama.292.21.2585 · Cited by 875 · see citing works
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Self-citationNiemi, M., Pasanen, M. K., & Neuvonen, P. J. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.002857 · Cited by 636 · see citing works
Shitara, Y., & Sugiyama, Y. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.03.003 · Cited by 574 · see citing works
Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia
Davidson, M. H., Mcgarry, T. F., Bettis, R. B., Melani, L., Lipka, L., LeBeaut, A., Suresh, R., Sun, S. H., & Veltri, E. P. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02610-4 · Cited by 557 · see citing works
SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid
Pasanen, M. K., Neuvonen, M., Neuvonen, P. J., & Niemi, M. (2006) · Pharmacogenetics and Genomics · doi:10.1097/01.fpc.0000230416.82349.90 · Cited by 470 · see citing works
Fruchart, J.-C., Sacks, F., Hermans, M. P., Assmann, G., Brown, W. V., Ceska, R., Chapman, M. J., Dodson, P. M., Fioretto, P., Ginsberg, H. N., et al. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.10.002 · Cited by 463 · see citing works
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Self-citationSafety considerations with fibrate therapy
Davidson, M. H., Armani, A., McKenney, J. M., & Jacobson, T. A. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.11.016 · Cited by 408 · see citing works
Shitara, Y., Hirano, M., Sato, H., & Sugiyama, Y. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.068536 · Cited by 407 · see citing works
EVALUATION OF DRUG-DRUG INTERACTION IN THE HEPATOBILIARY AND RENAL TRANSPORT OF DRUGS
Shitara, Y., Sato, H., & Sugiyama, Y. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121444 · Cited by 336 · see citing works
Wiggins, B. S., Saseen, J. J., Page, R. L., II, Reed, B. N., Sneed, K., Kostis, J. B., Lanfear, D. E., Virani, S. S., & Morris, P. B. (2016) · Circulation · doi:10.1161/cir.0000000000000456 · Cited by 339 · see citing works
Wilke, R. A., Ramsey, L. B., Johnson, S. G., Maxwell, W. D., McLeod, H. L., Voora, D., Krauss, R. M., Roden, D. M., Feng, Q., Cooper‐DeHoff, R. M., et al. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.57 · Cited by 332 · see citing works
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Kasiske, B., Cosío, F., Beto, J., Bolton, K., Chavers, B., Grimm, R., Levin, A., Masri, B., Parekh, R., Wanner, C., et al. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6135.2004.0355.x · Cited by 338 · see citing works
The effect of gemfibrozil on the pharmacokinetics of rosuvastatin
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Niemi, M., Backman, J. T., Neuvonen, M., & Neuvonen, P. J. (2003) · Diabetologia · doi:10.1007/s00125-003-1034-7 · Cited by 285 · see citing works
Self-citationMechanistic Studies on Metabolic Interactions between Gemfibrozil and Statins
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Melani, L. (2003) · European Heart Journal · doi:10.1016/s0195-668x(02)00803-5 · Cited by 271 · see citing works
Role of OATP Transporters in the Disposition of Drugs
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Self-citationGoldberg, A. C., Sapre, A., Liu, J., Capece, R., & Mitchel, Y. (2004) · Mayo Clinic Proceedings · doi:10.4065/79.5.620 · Cited by 191 · see citing works
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Wang, J.-S., Neuvonen, M., Wen, X., Backman, J. T., & Neuvonen, P. J. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.12.1352 · Cited by 189 · see citing works
Self-citationThe role of transporters in drug interactions
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Tenenbaum, A., & Fisman, E. Z. (2012) · Cardiovascular Diabetology · doi:10.1186/1475-2840-11-125 · Cited by 166 · see citing works
Backman, J. T., Luurila, H., Neuvonen, M., & Neuvonen, P. J. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.04.007 · Cited by 155 · see citing works
Self-citationSimvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle
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Pharmacologic characteristics of statins
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Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9.
Wen, X., Wang, J. S., Backman, J. T., Kivistö, K. T., & Neuvonen, P. J. (2001) · PubMed · Cited by 139 · see citing works
Self-citationSkottheim, I. B., Gedde‐Dahl, A., Hejazifar, S., Hoel, K., & Åsberg, A. (2008) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2007.12.009 · Cited by 137 · see citing works
Pitavastatin: Efficacy and Safety Profiles of A Novel Synthetic HMG‐CoA Reductase Inhibitor
Kajinami, K., Takekoshi, N., & Saito, Y. (2003) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2003.tb00116.x · Cited by 136 · see citing works
Gertz, M., Houston, J. B., & Galetin, A. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.039248 · Cited by 135 · see citing works
Davidson, M. H., Ballantyne, C. M., Kerzner, B., Melani, L., Sager, P. T., Lipka, L., Strony, J. T., Suresh, R., & Veltri, E. P. (2004) · International Journal of Clinical Practice · doi:10.1111/j.1368-5031.2004.00289.x · Cited by 135 · see citing works
Obach, R. S., Walsky, R. L., Venkatakrishnan, K., Houston, J. B., & Tremaine, L. M. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.09.004 · Cited by 134 · see citing works
Risk of adverse events with fibrates*
Alsheikh-Ali, A. A. A., Kuvin, J. T., & Karas, R. H. (2004) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2004.06.033 · Cited by 125 · see citing works
Statin myotoxicity: a review of genetic susceptibility factors
Needham, M., & Mastaglia, F. L. (2014) · Neuromuscular Disorders · doi:10.1016/j.nmd.2013.09.011 · Cited by 108 · see citing works
Fenofibrate: treatment of hyperlipidemia and beyond
Rosenson, R. S. (2008) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.6.10.1319 · Cited by 110 · see citing works
Fahrmayr, C., Fromm, M. F., & König, J. (2010) · Drug Metabolism Reviews · doi:10.3109/03602530903491683 · Cited by 108 · see citing works
Transporter-Mediated Drug-Drug Interactions and Their Significance
Liu, X. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-7647-4_5 · Cited by 109 · see citing works
Tenenbaum, A., & Fisman, E. Z. (2012) · Cardiovascular Diabetology · doi:10.1186/1475-2840-11-140 · Cited by 108 · see citing works
Carbamazepine markedly reduces serum concentrations of simvastatin and simvastatin acid
Uçar, M., Neuvonen, M., Luurila, H., Dahlqvist, R., Neuvonen, P. J., & Mj�rndal, T. (2004) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-003-0700-5 · Cited by 107 · see citing works
Learning from the cerivastatin experience
Farmer, J. A. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06489-3 · Cited by 105 · see citing works
Evans, M., & Rees, A. (2002) · Current Opinion in Lipidology · doi:10.1097/00041433-200208000-00009 · Cited by 104 · see citing works
Combination therapy for dyslipidemia: safety and regulatory considerations
Davidson, M. H. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02970-3 · Cited by 104 · see citing works
Igel, M., Sudhop, T., & von Bergmann, K. (2002) · The Journal of Clinical Pharmacology · doi:10.1177/009127002401102731 · Cited by 100 · see citing works
Bergman, A. J., Murphy, G., Burke, J., Zhao, J. J., Valesky, R., Liu, L., Lasseter, K. C., He, W., Prueksaritanont, T., Qiu, Y., et al. (2004) · The Journal of Clinical Pharmacology · doi:10.1177/0091270004268044 · Cited by 97 · see citing works
Thibaut, R., Schnell, S., & Porte, C. (2006) · Environmental Science & Technology · doi:10.1021/es0607483 · Cited by 96 · see citing works
Niemi, M., Kajosaari, L. I., Neuvonen, M., Backman, J. T., & Neuvonen, P. J. (2004) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.02027.x · Cited by 95 · see citing works
Self-citationYamazaki, M., LI, B., Louie, S. W., Pudvah, N. T., Stocco, R., Wong, W., Abramovitz, M., Demartis, A., Laufer, R., Hochman, J. H., et al. (2005) · Xenobiotica · doi:10.1080/00498250500136676 · Cited by 95 · see citing works
Tornio, A., Niemi, M., Neuvonen, M., Laitila, J., Kalliokoski, A., Neuvonen, P. J., & Backman, J. T. (2008) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2008.34 · Cited by 92 · see citing works
Self-citationNiemi, M., Tornio, A., Pasanen, M. K., Fredrikson, H., Neuvonen, P. J., & Backman, J. T. (2006) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-006-0133-z · Cited by 88 · see citing works
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Paoletti, R., Corsini, A., & Bellosta, S. (2002) · Atherosclerosis Supplements · doi:10.1016/s1567-5688(02)00002-8 · Cited by 85 · see citing works
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McKenney, J. M. (2005) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/62.10.1033 · Cited by 83 · see citing works
Fibrates in Combination With Statins in the Management of Dyslipidemia
Jacobson, T. A., & Zimmerman, F. H. (2006) · Journal of Clinical Hypertension · doi:10.1111/j.1524-6175.2005.05278.x · Cited by 82 · see citing works
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Jackevicius, C. A. (2011) · JAMA · doi:10.1001/jama.2011.353 · Cited by 82 · see citing works
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Hirota, T., & Ieiri, I. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2015.1056149 · Cited by 84 · see citing works
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Tiwari, A. K., Bansal, V. S., Chugh, A., & Mookhtiar, K. A. (2006) · Expert Opinion on Drug Safety · doi:10.1517/14740338.5.5.651 · Cited by 80 · see citing works
Skaletz‐Rorowski, A. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00618-1 · Cited by 79 · see citing works
Roles of Exercise and Pharmacokinetics in Cerivastatin-Induced Skeletal Muscle Toxicity
Seachrist, J. L., Loi, C., Evans, M. G., Criswell, K. A., & Rothwell, C. E. (2005) · Toxicological Sciences · doi:10.1093/toxsci/kfi305 · Cited by 77 · see citing works
Davidson, M. H. (2005) · Expert Opinion on Drug Safety · doi:10.1517/14740338.5.1.145 · Cited by 76 · see citing works
In vitroevidence for the role of OATP and OCT uptake transporters in drug–drug interactions
Kindla, J., Fromm, M. F., & König, J. (2009) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425250902911463 · Cited by 74 · see citing works
Hinton, L. K., Galetin, A., & Houston, J. B. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9446-6 · Cited by 73 · see citing works
Comparative Effects of Fibrates on Drug Metabolizing Enzymes in Human Hepatocytes
Prueksaritanont, T., Richards, K. M., Qiu, Y., Strong-Basalyga, K., Miller, A. R., Li, C., Eisenhandler, R., & Carlini, E. J. (2005) · Pharmaceutical Research · doi:10.1007/s11095-004-9011-5 · Cited by 73 · see citing works
Re, M. D., Fogli, S., Derosa, L., Massari, F., SOUZA, P. D., Crucitta, S., Sergio Bracarda, A., Santini, D., & Danesi, R. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.03.001 · Cited by 70 · see citing works
Varma, M. V. S., Lin, J., Bi, Y., Kimoto, E., & Rodrigues, A. D. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.064303 · Cited by 69 · see citing works
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Becquemont, L., Neuvonen, M., Verstuyft, C., Jaillon, P., Letierce, A., Neuvonen, P. J., & Funck‐Brentano, C. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100098 · Cited by 64 · see citing works
Fibrates: What Have We Learned in the Past 40 Years?
Backes, J. M., Gibson, C., Ruisinger, J. F., & Moriarty, P. M. (2007) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.27.3.412 · Cited by 63 · see citing works
Wang, J., Li, X., Sun, X., Li, G., Sun, J., Ye, Y., Cong, L., Li, W., Lu, S., Feng, J., et al. (2018) · Cancer Science · doi:10.1111/cas.13570 · Cited by 61 · see citing works
Combination statin-fibrate therapy: safety aspects
Franssen, R., Vergeer, M., Stroes, E. S. G., & Kastelein, J. J. P. (2009) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.00917.x · Cited by 60 · see citing works
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Τζιόμαλος, Κ., & Athyros, V. G. (2006) · International Journal of Nanomedicine · doi:10.2147/nano.2006.1.2.129 · Cited by 58 · see citing works
Role of transport proteins in drug discovery and development: a pharmaceutical perspective
Ayrton, A. D., & Morgan, P. (2008) · Xenobiotica · doi:10.1080/00498250801923855 · Cited by 58 · see citing works
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Self-citationSchuster, H. (2003) · Cardiology · doi:10.1159/000070669 · Cited by 55 · see citing works
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Whitfield, L. R., Porcari, A. R., Alvey, C. W., Abel, R. B., Bullen, W., & Hartman, D. (2010) · The Journal of Clinical Pharmacology · doi:10.1177/0091270010366446 · Cited by 54 · see citing works
Sharma, P. K., Butters, C., Smith, V., Elsby, R., & Surry, D. D. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.04.003 · Cited by 53 · see citing works
Fenner, K. S., Jones, H. M., Ullah, M., Kempshall, S., Dickins, M., Lai, Y., Morgan, P., & Barton, H. A. (2011) · Xenobiotica · doi:10.3109/00498254.2011.626464 · Cited by 53 · see citing works
Goosen, T. C., Bauman, J. N., Davis, J. A., Yu, C., Hurst, S. I., Williams, J. A., & Loi, C. (2007) · Drug Metabolism and Disposition · doi:10.1124/dmd.107.015230 · Cited by 52 · see citing works
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Davidson, M. H., & Robinson, J. G. (2006) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.7.13.1701 · Cited by 51 · see citing works
Murtola, T. J., Pennanen, P. T., Syvälä, H., Bläuer, M., Ylikomi, T. J., & Tammela, T. L. J. (2009) · The Prostate · doi:10.1002/pros.20951 · Cited by 49 · see citing works
Xu, Y., Zhou, Y., Hayashi, M., Shou, M., & Skiles, G. L. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.038067 · Cited by 47 · see citing works
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Khurana, V., Minocha, M., Pal, D., & Mitra, A. K. (2014) · Drug metabolism and drug interactions · doi:10.1515/dmdi-2013-0062 · Cited by 46 · see citing works
Role of gemfibrozil as an inhibitor of CYP2C8 and membrane transporters
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Self-citationBernsdorf, A., Gießmann, T., Modeß, C., Wegner, D., Igelbrink, S., Hecker, U., Haenisch, S., Cascorbi, I., Terhaag, B., & Siegmund, W. (2006) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2006.02599.x · Cited by 45 · see citing works
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Shyamsundar, M., McAuley, D. F., Shields, M. O., MacSweeney, R. E., Duffy, M. J., Johnston, J. R., McGuigan, J., Backman, J. T., Calfee, C. S., Matthay, M. A., et al. (2013) · Annals of Surgery · doi:10.1097/sla.0b013e31829d686b · Cited by 45 · see citing works
Self-citationA Neuromuscular Approach to Statin-Related Myotoxicity
Baker, S. K., & Samjoo, I. A. (2008) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100007514 · Cited by 45 · see citing works
- Authors
- Backman, J.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Backman, J
- ORCID
- Backman, J
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2000-08
- Volume
- 68
- Issue
- 2
- Pages
- 122-129
- ISSN
- 0009-9236 (ISSN-L)
- OpenAlex
- W1985258130
- Cited by
- 264
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 5 · 2019: 10 · 2018: 2 · 2017: 5 · 2016: 8 · 2015: 15 · 2014: 10 · 2013: 11 · 2012: 12
- FWCI
- 10.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- simvastatin, gemfibrozil, simvastatin acid, drug-drug interactions, pharmacokinetics, CYP3A4, myopathy, statins, fibrates, midazolam 1'-hydroxylation, elimination half-life
- MeSH terms
- Adult, Hypolipidemic Agents, Double-Blind Method, Drug Interactions, Enzyme Inhibitors, Female, Humans, Male, Microsomes, Liver, Gemfibrozil, Cross-Over Studies, Simvastatin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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