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Hepatotoxic Medication

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21. Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet! Full Text available with Trip Pro

Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet! One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity.We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg (...) /day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB). In an intracellular Mycobacterium tuberculosis (Mtb) HFS-TB experiment, we added a 3-dimensional human organotypic liver to determine potential hepatotoxicity of the high-dose regimen, based on lactate dehydrogenase (LDH). Treatment lasted 28 days

2018 Clinical Infectious Diseases

22. A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations Full Text available with Trip Pro

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating (...) toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes

2017 PLoS computational biology

23. Connexin-based signaling and drug-induced hepatotoxicity Full Text available with Trip Pro

Connexin-based signaling and drug-induced hepatotoxicity Being critical mediators of liver homeostasis, connexins and their channels are frequently involved in liver toxicity. In the current paper, specific attention is paid to actions of hepatotoxic drugs on these communicative structures. In a first part, an overview is provided on the structural, regulatory and functional properties of connexin-based channels in the liver. In the second part, documented effects of acetaminophen (...) , hypolipidemic drugs, phenobarbital and methapyriline on connexin signaling are discussed. Furthermore, the relevance of this subject for the fields of clinical and in vitro toxicology is demonstrated.

2017 Journal of clinical and translational research

24. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity Full Text available with Trip Pro

these pharmaceuticals are particularly hepatotoxic in obesity and NAFLD. Other drugs such as pentoxifylline, phenobarbital and omeprazole might also pose a risk but more investigations are required to determine whether this risk is significant or not. Because obese people often take several drugs for the treatment of different obesity-related diseases such as type 2 diabetes, hyperlipidemia and coronary heart disease, it is urgent to identify the main pharmaceuticals that can cause acute hepatitis on a fatty liver (...) Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity Obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which refers to a large spectrum of hepatic lesions including fatty liver, nonalcoholic steatohepatitis (NASH) and cirrhosis. Different investigations showed or suggested that obesity and NAFLD are able to increase the risk of hepatotoxicity of different drugs. Some of these drugs could induce more frequently an acute hepatitis

2017 Journal of clinical and translational research

25. Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae Full Text available with Trip Pro

Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used (...) shows that administering compounds into the yolk is relevant in the framework of hepatotoxicity testing. Taken together, cell imaging counting provides a novel and rapid tool for screening hepatotoxicants in early stages of drug development. This method is also suitable for testing of other organ-related toxicities subject to the organs and tissues expressing fluorescent proteins in transgenic zebrafish lines.

2017 International journal of molecular sciences

26. Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back–Looking Forward to Next-Generation Innovation Full Text available with Trip Pro

Genome-Wide Association Studies for Idiosyncratic Drug-Induced Hepatotoxicity: Looking Back–Looking Forward to Next-Generation Innovation Idiosyncratic drug-induced hepatotoxicity is a formidable challenge for rational drug discovery and development, as well as the science of personalized medicine. There is evidence that hereditary factors, in part, contribute to drug toxicity. This expert analysis and review offer the insights gained, and the challenges ahead, for genome-wide association (...) studies (GWASs) of idiosyncratic drug-induced hepatotoxicity. Published articles on genome-wide and subsequent replication studies were systematically searched in the PubMed electronic database. We found that the genetic risk variants that were identified genome-wide, and replication confirmed, are mainly related to polymorphisms in the human leukocyte antigen (HLA) region that include HLA-DQB1*06:02 for amoxicillin-clavulanate, HLA-B*57:01 for flucloxacillin, HLA-DRB1*15:01 for lumiracoxib, and HLA

2017 Omics : a journal of integrative biology

27. Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs Full Text available with Trip Pro

Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV- and ARV-ATD-induced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub (...) -Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients. Treatment-naïve newly diagnosed HIV patients (n = 719) with or without tuberculosis (TB) co-infection were enrolled prospectively and received efavirenz-based ARV therapy with or without rifampicin-based short course ATD, respectively. Whole-genome genotyping

2017 Omics : a journal of integrative biology

28. Two-photon fluorescent probe for revealing drug-induced hepatotoxicity via mapping fluctuation of peroxynitrite †Electronic supplementary information (ESI) available: Detailed experimental procedures, mass spectra, figures, tables and NMR spectra. See D Full Text available with Trip Pro

Two-photon fluorescent probe for revealing drug-induced hepatotoxicity via mapping fluctuation of peroxynitrite †Electronic supplementary information (ESI) available: Detailed experimental procedures, mass spectra, figures, tables and NMR spectra. See D Drug-induced injury has attracted increasing attention in public health issues. Among them, hepatotoxicity has been regarded as the leading clinical problem caused by drug toxicity. However, owing to the complexity of the involved (...) pathophysiological mechanisms and the lack of noninvasive, straightforward, and real-time tools, drug-induced hepatotoxicity has rarely been predicted satisfactorily. In this paper, by utilizing the reactive species peroxynitrite (ONOO-) as a biomarker, we present a two-photon fluorescent probe, TP-KA, holding rapid response, high specificity and sensitivity towards ONOO-, to investigate drug (acetaminophen and tolcapone)-related liver injury and the remediate effect of N-acetyl cysteine (NAC). With the support

2017 Chemical Science

29. Paper supported long-term 3D liver co-culture model for the assessment of hepatotoxic drugs †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7tx00209b Full Text available with Trip Pro

Paper supported long-term 3D liver co-culture model for the assessment of hepatotoxic drugs †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7tx00209b Preservation of hepatic phenotype and functions in vitro has always been a great challenge for the reconstruction of liver tissue engineering and in pharmaceutical research studies. Human induced hepatocytes (hiHeps) generated from fibroblasts can be reproducible with almost normal levels of liver specific functions (...) , which are considered as a new source of hepatocytes for biomedical applications. Moreover, paper has served as an attractive biocompatible material for cell-based applications. In this study, we established a simple paper-based scaffold array for creating a 3D liver co-culture model that enabled the assessment of drug induced hepatotoxicity. The hiHeps co-cultured with HUVECs exhibited a 3D like morphology and maintained the liver specific functions of producing albumin and urea for up to 2 months

2017 Toxicology research

30. Prediction models for drug-induced hepatotoxicity by using weighted molecular fingerprints Full Text available with Trip Pro

Prediction models for drug-induced hepatotoxicity by using weighted molecular fingerprints Drug-induced liver injury (DILI) is a critical issue in drug development because DILI causes failures in clinical trials and the withdrawal of approved drugs from the market. There have been many attempts to predict the risk of DILI based on in vivo and in silico identification of hepatotoxic compounds. In the current study, we propose the in silico prediction model predicting DILI using weighted (...) in natural herbs and their increased application in drug development, DILI labeling would be very important.

2017 BMC bioinformatics

31. Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs Full Text available with Trip Pro

Strategies for In Vivo Screening and Mitigation of Hepatotoxicity Associated with Antisense Drugs Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent (...) hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs. To rank ASOs based on their effect on the liver, we have developed an acute screen in the mouse that can be applied early in the drug development cycle. A single-dose (3-day) screen with streamlined endpoints (i.e., plasma transaminase levels and liver weights) was observed to be predictive of ASO hepatotoxicity ranking established

2017 Molecular therapy. Nucleic acids

32. Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity Full Text available with Trip Pro

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs.This is a prospective, randomized, double-blind (...) silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.

2017 Tuberculosis and respiratory diseases Controlled trial quality: predicted high

33. Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats Full Text available with Trip Pro

Herb-Drug Interaction between the Traditional Hepatoprotective Formulation and Sorafenib on Hepatotoxicity, Histopathology and Pharmacokinetics in Rats Sorafenib has been used as a standard therapy for advanced hepatocellular carcinoma (HCC). In Asia, patients with HCC are potentially treated with the combination of sorafenib and Chinese herbal medicines to improve the efficiency and reduce the side effects of sorafenib. However, limited information about the herb-drug interactions is available (...) . We hypothesize that the Chinese herbal medicine may exert hepatoprotective effects on the sorafenib-treated group. The aim of this study is to investigate the pharmacokinetic mechanism of drug-drug interactions of sorafenib including interacting with hepatoprotective formulation, Long-Dan-Xie-Gan-Tang formulation (LDXGT) and with two cytochrome P450 3A4 (CYP3A4) inhibitors, grapefruit juice and ketoconazole. Liver enzyme levels and histopathology of liver slices were used to evaluate sorafenib

2017 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry

34. Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project Full Text available with Trip Pro

Hepatotoxicity with Vismodegib: An MD Anderson Cancer Center and Research on Adverse Drug Events and Reports Project On 30 January 2012, the US FDA approved vismodegib (Erivedge®, Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma.Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers.FAERS (...) of Northwestern University were searched.Two cases of severe liver dysfunction were published (Common Terminology Criteria for Adverse Events [CTCAE] class III), and 94 reports of adverse events (AEs) were detected in FAERS, 35 of which were serious AEs. Safety notifications related to hepatotoxicity have not been issued by the manufacturer or the FDA, although vismodegib is listed in LiverTox and the European Medicines Agency website.We identified a detectable safety signal for hepatotoxicity for vismodegib

2017 Drugs in R&D

35. Hepatotoxicity and Drug/Chemical Interaction Toxicity of Nanoclay Particles in Mice Full Text available with Trip Pro

Hepatotoxicity and Drug/Chemical Interaction Toxicity of Nanoclay Particles in Mice Nanomaterials are relatively new and unconventional materials with many useful properties, but their effects on biological systems are poorly understood. Nanoclay is a general term for layered mineral silicate nanoparticles that are ideally suited for use in clay-based nanocomposites. The potential biological hazards of nanoclays have not been addressed, however. Therefore, we investigated the in vivo effects (...) and drug interactions of nanoclays. In mice, administration of nanoclay particles via the tail vein led to acute liver injury. Co-administration of nanoclay and carbon tetrachloride, paraquat, or cisplatin resulted in both liver and kidney injury. Our findings thus indicate that nanoclay particles are potentially hepato- and nephrotoxic.

2017 Nanoscale research letters

36. Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications Full Text available with Trip Pro

Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture (...) , endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver-resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured

2018 Biotechnology and bioengineering

37. Pharmacokinetics of Schizandrin and Its Pharmaceutical Products Assessed Using a Validated LC–MS/MS Method Full Text available with Trip Pro

Pharmacokinetics of Schizandrin and Its Pharmaceutical Products Assessed Using a Validated LC–MS/MS Method Schisandra chinensis has been used as an important component in various prescriptions in traditional Chinese medicine and, more recently, in Western-based medicine for its anti-hepatotoxic effect. The aim of this study was to develop a selective, rapid, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method for pharmacokinetic studies of schizandrin in rats (...) of schizandrin was approximately 15.56 ± 10.47% in rats, however the oral bioavailability of herbal extract was higher than single compound. The method was successfully applied to the pharmacokinetic study of pure schizandrin after oral administration of its pharmaceutical industry products in rats.

2018 Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry

38. Drug-Induced Liver Injury

andpathologicalphenotypesandthecurrentabsenceofspeci?c biomarkers. This makes the diagnosis of drug-induced liver injury an uncertain process, requiring a high degree of aware- ness of the condition and the careful exclusion of alternative aetiologies of liver disease. Idiosyncratic hepatotoxicity can be severe, leading to a particularly serious variety of acute liver failure for which no effective therapy has yet been developed. These Clinical Practice Guidelines summarize the available evi- dence on risk factors, diagnosis, management and risk (...) . Clinical trials produce reliable information about the devel- opment of abnormal liver biochemistries and DILI if the inci- dence is high. However, such trials usually include a limited number of patients and are therefore underpowered to detect rare adverse effects such as idiosyncratic hepatotoxicity. Conse- quently,themajorityofdataareprovidedbyretrospectivestud- ies of databases from pharmacovigilance centres and/or pharmaceutical companies, aimed to determine the most fre- quently associated drugs

2019 European Association for the Study of the Liver

39. Systematic reviews of the hepatotoxic effects of specified compounds/drugs as observed in humans and experimental animals (rats, mice, dogs and non-human primates)

Systematic reviews of the hepatotoxic effects of specified compounds/drugs as observed in humans and experimental animals (rats, mice, dogs and non-human primates) Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g (...) . Combination therapy or contamination 6. Not about analgesics used in the clinic Full text-screening: As above, with the addition of: 7. No relevant outcome measure reported ">Prioritise the exclusion criteria Example: Two reviewers will independently extract data from each article. We first try to extract numerical data from tables, text or figures. If these are not reported, we will extract data from graphs using digital ruler software. In case data are not reported or unclear, we will attempt to contact

2018 PROSPERO

40. Hepatotoxic Medication

Medication Aka: Hepatotoxic Medication , Hepatotoxic Supplement , Hepatotoxin From Related Chapters II. Causes: Medications associated with Cirrhosis Alpha- (no longer available in United States) III. Causes: Most common drug causes of Acute Hepatitis -Clavulanic Acid ( , most common cause) (AST often rises above 5000, most common cause of in U.S.) Anti- medications Trimethoprim-sulfamethoxazole (mimics ) (mimics ) IV. Causes: Hepatotoxic Medications (including mild transaminase elevations) s s Avoid (...) Hepatotoxic Medication Hepatotoxic Medication Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Hepatotoxic Medication Hepatotoxic

2018 FP Notebook

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