ArticleOncotarget2015
A comprehensive study of the association between drug hepatotoxicity and daily dose, liver metabolism, and lipophilicity using 975 oral medications.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Hepatotoxicity and efficacy associated with first- and new-generation EGFR-TKIs in patients with NSCLC: a systematic review and meta-analysis.BMC cancer · 2025Pooled it
- Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.JAMA network open · 2021Pooled it
- Drug-induced liver injury: a comprehensive review.Therapeutic advances in gastroenterology · 2023Review
- Carba Analogues of Flupirtine and Retigabine with Improved Oxidation Resistance and Reduced Risk of Quinoid Metabolite Formation.ChemMedChem · 2022Article
- Herb-Induced Liver Injury-A Challenging Diagnosis.Healthcare (Basel, Switzerland) · 2022Review
- Study on the Characteristics of Small-Molecule Kinase Inhibitors-Related Drug-Induced Liver Injury.Frontiers in pharmacology · 2022Article
- The LiverTox Paradox-Gaps between Promised Data and Reality Check.Diagnostics (Basel, Switzerland) · 2021Article
- Imipramine Accelerates Nonalcoholic Fatty Liver Disease, Renal Impairment, Diabetic Retinopathy, Insulin Resistance, and Urinary Chromium Loss in Obese Mice.Veterinary sciences · 2021Article
- Idiosyncratic Drug Induced Liver Injury, Cytochrome P450, Metabolic Risk Factors and Lipophilicity: Highlights and Controversies.International journal of molecular sciences · 2021Review
- Effects of medium- and long-chain fatty acids on acetaminophen- or rifampicin-induced hepatocellular injury.Food science & nutrition · 2020Article
- Machine-Learning Prediction of Oral Drug-Induced Liver Injury (DILI) via Multiple Features and Endpoints.BioMed research international · 2020Article
- Strategies for Early Prediction and Timely Recognition of Drug-Induced Liver Injury: The Case of Cyclin-Dependent Kinase 4/6 Inhibitors.Frontiers in pharmacology · 2019Review
- Effects of 31 FDA approved small-molecule kinase inhibitors on isolated rat liver mitochondria.Archives of toxicology · 2017Article
- Associations of Drug Lipophilicity and Extent of Metabolism with Drug-Induced Liver Injury.International journal of molecular sciences · 2017Article
- Carboplatin-induced hematotoxicity among patients with non-small cell lung cancer: Analysis on clinical adverse events and drug-gene interactions.Oncotarget · 2017Article
- Incidence and physiological mechanism of carboplatin-induced electrolyte abnormality among patients with non-small cell lung cancer.Oncotarget · 2017Article
- Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity.Journal of clinical and translational research · 2017Article
- Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases.Oncotarget · 2016Article
- Drug discovery using clinical outcome-based Connectivity Mapping: application to ovarian cancer.BMC genomics · 2016Article
- Toxicological Differences Between NMDA Receptor Antagonists and Cholinesterase Inhibitors.American journal of Alzheimer's disease and other dementias · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It was recently suggested that daily dose, liver metabolism and lipophilicity were associated with an oral drug's potential to cause hepatotoxicity, but this has not been widely accepted. A likely reason is that published data lack comprehensiveness, as they were based on only about one third of all FDA approved single-active-ingredient oral prescription drugs. Here the 975 oral drugs used worldwide which have a Defined Daily Dose (DDD) designated in the World Health Organization's Anatomical Therapeutic Chemical classification system and whose hADRs potential and metabolism data are available in the Micromedex Drugdex® compendium were studied, with their lipophilicity calculated by the partition coefficient LogP. Of the 975 drugs examined, 49% (478) have the potential to induce at least one type of hepatic adverse drug reactions (hADRs) such as fatal hepatotoxicity, acute liver failure, significant ALT/AST elevation, hepatitis, and jaundice. By single factor analysis, a higher DDD (≥100 mg) was found to be associated with all types of hADRs, and extensive liver metabolism (≥50%) was associated with a subset of hADRs including fatal hADRs, hepatitis and jaundice, while LogP showed no relation to any types of hADRs. Contrary to previous reports, none of the combination, neither DDD and liver metabolism, nor DDD and LogP, was found to be more predictive of hADRs than using DDD or liver metabolism alone. These data provide convincing evidence that a higher daily dose and extensive liver metabolism, but not lipophilicity, are independent but not synergistic risk factors for oral drugs to induce hepatotoxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.