650 results match your criteria Isoniazid Hepatotoxicity


Tolerability of Isoniazid Preventive Therapy in an HIV-Infected Cohort of Paediatric and Adolescent Patients on Antiretroviral Therapy from a Resource-Limited Setting: A Retrospective Cohort Study.

Drugs Real World Outcomes 2019 Feb 13. Epub 2019 Feb 13.

Newlands Clinic, 56 Enterprise Road, Highlands, Harare, Zimbabwe.

Background: Treating patients with latent tuberculosis infection (LTBI) to prevent development of active disease is an essential strategy for eliminating TB. There are concerns regarding the use of isoniazid due to the potential for hepatotoxicity. This study was conducted to determine the incidence of adverse hepatic events after isoniazid preventive therapy (IPT) commencement in a cohort of HIV-infected paediatric and adolescent patients on antiretroviral therapy (ART). Read More

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http://link.springer.com/10.1007/s40801-019-0147-3
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http://dx.doi.org/10.1007/s40801-019-0147-3DOI Listing
February 2019
4 Reads

Three-month weekly rifapentine plus isoniazid for tuberculosis preventive treatment: a systematic review.

Int J Tuberc Lung Dis 2018 Dec;22(12):1422-1428

Global TB Programme.

Background: Uptake of preventive treatment for tuberculosis (TB) remains poor. A 3-month regimen of rifapentine (RPT) plus isoniazid (INH) (3HP) could facilitate its scale-up. We conducted a systematic review to assess the effects of 3HP compared with daily 6- or 9-month INH monotherapy. Read More

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http://dx.doi.org/10.5588/ijtld.18.0168DOI Listing
December 2018

Biodistribution of Tc-99m Labeled Isoniazid Solid Lipid Nanoparticles in Wistar Rats.

Iran J Pharm Res 2018 ;17(4):1209-1216

Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alta, Canada.

In this study Isoniazid (INH) as one of the first line drugs in treatment of Tuberculosis was investigated to be loaded in Solid Lipid Nanoparticles (SLNs) for reducing hepatotoxicity as well as prolonging drug release. High shear homogenization method was performed to prepare INH SLNs. To compare biodistribution of INH before and after loading in SLNs, INH was labeled by Technetium 99 (Tc99) after derivatization. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269554PMC
January 2018

Telfairia occidentalis (Cucurbitaceae) pulp extract mitigates rifampicin-isoniazid-induced hepatotoxicity in an in vivo rat model of oxidative stress.

J Integr Med 2019 Jan 1;17(1):46-56. Epub 2018 Dec 1.

Medical Laboratory Sciences, Faculty of Basic Medical Sciences, College of Health Sciences, Niger Delta University, Amassoma, PMB 071 Yenegoa, Bayelsa State, Nigeria.

Objective: Drug-induced liver injury complicates antituberculosis drug treatment and is a leading cause of death worldwide. The aim of this study is to establish the ethnomedicinal claim of hepatoprotective effects of fruit pulp extract of Telfairia occidentalis against rifampicin (RIF) and isoniazid (INH)-induced oxidative stress in rats.

Methods: T. Read More

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http://dx.doi.org/10.1016/j.joim.2018.11.008DOI Listing
January 2019
5 Reads

Mitochondrial dysfunction as a mechanism of drug-induced hepatotoxicity: current understanding and future perspectives.

J Clin Transl Res 2018 28;4(1). Epub 2018 May 28.

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, US.

Mitochondria are critical cellular organelles for energy generation and are now also recognized as playing important roles in cellular signaling. Their central role in energy metabolism, as well as their high abundance in hepatocytes, make them important targets for drug-induced hepatotoxicity. This review summarizes the current mechanistic understanding of the role of mitochondria in drug-induced hepatotoxicity caused by acetaminophen, diclofenac, anti-tuberculosis drugs such as rifampin and isoniazid, anti-epileptic drugs such as valproic acid and constituents of herbal supplements such as pyrrolizidine alkaloids. Read More

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http://dx.doi.org/10.18053/jctres.04.201801.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261533PMC
May 2018
4 Reads

Revised Antituberculosis Drug Doses and Hepatotoxicity in HIV Negative Children.

Indian J Pediatr 2018 Dec 4. Epub 2018 Dec 4.

Department of Pediatrics, St John's Medical College Hospital, Bengaluru, Karnataka, India.

Objectives: To compare the incidence of anti tuberculosis drug-induced hepatotoxicity (ATDH) with those on old vs. revised WHO doses in human immunodeficiency virus (HIV) negative children. The secondary objective was to determine the overall incidence of hepatitis in children on Anti tubercular treatment (ATT) and isoniazid prophylactic therapy (IPT). Read More

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http://link.springer.com/10.1007/s12098-018-2812-z
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http://dx.doi.org/10.1007/s12098-018-2812-zDOI Listing
December 2018
8 Reads

Pharmacogenetic association between gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence.

Biosci Rep 2019 Jan 15;39(1). Epub 2019 Jan 15.

Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia

Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 () gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. Read More

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http://bioscirep.org/lookup/doi/10.1042/BSR20180845
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http://dx.doi.org/10.1042/BSR20180845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331676PMC
January 2019
9 Reads
2.637 Impact Factor

Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!

Clin Infect Dis 2018 Nov;67(suppl_3):S359-S364

Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.

Background: 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.

Methods: 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). Read More

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http://dx.doi.org/10.1093/cid/ciy627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260156PMC
November 2018
5 Reads

Metabolomic Study to Determine the Mechanism Underlying the Effects of Polysaccharide on Isoniazid- and Rifampicin-Induced Hepatotoxicity in Mice.

Molecules 2018 Nov 27;23(12). Epub 2018 Nov 27.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100102, China.

In this study, a non-targeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was used to characterize the plasma metabolic profile associated with the protective effects of the polysaccharide (SSP) on isoniazid (INH)-and rifampicin (RFP)-induced hepatotoxicity in mice. Fourteen potential biomarkers were identified from the plasma of SSP-treated mice. The protective effects of SSP on hepatotoxicity caused by the combination of INH and RFP (INH/RFP) were further elucidated by investigating the related metabolic pathways. Read More

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http://dx.doi.org/10.3390/molecules23123087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321494PMC
November 2018
13 Reads

Short-course regimens of rifapentine plus isoniazid to treat latent tuberculosis infection in older Chinese patients: a randomised controlled study.

Eur Respir J 2018 Dec 20;52(6). Epub 2018 Dec 20.

MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for Tuberculosis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Latent tuberculosis infection (LTBI) management is now a critical component of the World Health Organization's End TB Strategy.In this randomised controlled trial (Chinese Clinical Trial Registry identifier ChiCTR-IOR-15007202), two short-course regimens with rifapentine plus isoniazid (a 3-month once-weekly regimen and a 2-month twice-weekly regimen) were initially designed to be evaluated for rural residents aged 50-69 years with LTBI in China.Due to the increasingly rapid growth and unexpected high frequency of adverse effects, the treatments were terminated early (after 8 weeks for the once-weekly regimen and after 6 weeks for the twice-weekly regimen). Read More

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http://dx.doi.org/10.1183/13993003.01470-2018DOI Listing
December 2018
25 Reads

Sagittaria sagittifolia polysaccharide protects against isoniazid- and rifampicin-induced hepatic injury via activation of nuclear factor E2-related factor 2 signaling in mice.

J Ethnopharmacol 2018 Dec 5;227:237-245. Epub 2018 Sep 5.

Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. Electronic address:

Ethnopharmacological Relevance: The Sagittaria sagittifolia L. polysaccharide (SSP) is a purified form of a homogeneous polysaccharide isolated from the root tubers of S. sagittifolia, which has been used as a protectant against hepatotoxicity induced by coadministration of isoniazid and rifampicin. Read More

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http://dx.doi.org/10.1016/j.jep.2018.09.002DOI Listing
December 2018
21 Reads

Effects of preventive therapy for latent tuberculosis infection and factors associated with treatment abandonment: a cross-sectional study.

J Thorac Dis 2018 Jul;10(7):4377-4386

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515 China.

Background: Routine data on the use of preventive therapy (PT) for latent tuberculosis infection (LTBI) in students are scarce in high tuberculosis (TB) burden countries. This study aimed to investigate the effects of PT and identify factors related to PT abandonment during the school TB epidemic in Guangzhou, southern China.

Methods: Purified protein derivative (PPD) skin testing was performed on all staff and students in a vocational school in Guangzhou, southern China during December 2014. Read More

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http://dx.doi.org/10.21037/jtd.2018.06.138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105962PMC
July 2018
2 Reads

Hold the Gaba: A Case of Gabapentin-induced Hepatotoxicity.

Cureus 2018 Mar 4;10(3):e2269. Epub 2018 Mar 4.

Internal Medicine, Mercy Clinic Internal Medicine, St Louis, USA.

A drug-induced liver injury is one of the most common causes of acute liver failure. While acetaminophen is the most common etiology, other offending medications include amoxicillin-clavulanic acid, amiodarone, isoniazid, and fluoroquinolones to name a few. Gabapentin, a gamma-aminobutyric acid (GABA) analogue, has infrequently been reported to cause liver injury; however, the causality in the previous reports is contested. Read More

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http://dx.doi.org/10.7759/cureus.2269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093755PMC
March 2018
14 Reads

Amelioration of hepatotoxicity by biocleavable aminothiol chimeras of isoniazid: Design, synthesis, kinetics and pharmacological evaluation.

World J Hepatol 2018 Jul;10(7):496-508

Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth University, Maharashtra 411038, India.

Aim: To overcome the hazardous effects on liver caused by long-term use of antitubercular agent isoniazid (INH) by developing a novel hepatoprotective prodrug strategy by conjugating INH with aminothiols as antioxidant promoities for probable synergistic effect.

Methods: INH was conjugated with N-acetyl cysteine (NAC) and N-(2)-mercaptopropionyl glycine using the Schotten-Baumann reaction and with L-methionine using Boc-anhydride through a biocleavable amide linkage. Synthesized prodrugs were characterized by spectral analysis, and and release studies were carried out using HPLC. Read More

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http://dx.doi.org/10.4254/wjh.v10.i7.496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068850PMC

Serious hepatotoxicity following use of isoniazid preventive therapy in HIV patients in Eritrea.

Pharmacol Res Perspect 2018 07 31;6(4):e00423. Epub 2018 Jul 31.

Keren Zonal Referral Hospital Keren Eritrea.

WHO information note indicates that isoniazid preventive therapy (IPT) is generally safe with little risk of hepatotoxicity. However, when the policy of IPT for HIV patients was introduced in Eritrea, frequent IPT-associated hepatotoxicity and fatality have been reported to the Pharmacovigilance Centre. The aim of the study is to assess the causal association of IPT and hepatotoxicity and identify possible risk factors in patients on Highly Active Anti-retroviral Therapy (HAART). Read More

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http://doi.wiley.com/10.1002/prp2.423
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http://dx.doi.org/10.1002/prp2.423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066797PMC
July 2018
5 Reads

Dysregulation of BSEP and MRP2 May Play an Important Role in Isoniazid-Induced Liver Injury via the SIRT1/FXR Pathway in Rats and HepG2 Cells.

Biol Pharm Bull 2018 ;41(8):1211-1218

Department of Pharmacy, The First Hospital of Jilin University.

To explore the role of the abnormal expression of the bile salt export pump (BSEP) and multidrug resistance protein 2 (MRP2) in isoniazid (INH)-induced liver injury, we assessed the liver injury induced by INH in rats and HepG2 cells in vitro. The regulatory pathways via Sirtuin 1 (SIRT1) and farnesoid X receptor (FXR) were also determined. Rat liver injury was assessed by histopathological and biochemical analysis and HepG2 cytotoxicity was assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Read More

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http://dx.doi.org/10.1248/bpb.b18-00028DOI Listing
October 2018
3 Reads

Twelve-dose weekly rifapentine plus isoniazid for latent tuberculosis infection: A multicentre randomised controlled trial in Taiwan.

Tuberculosis (Edinb) 2018 07 7;111:121-126. Epub 2018 Jun 7.

Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Treatment of latent tuberculosis (TB) infection (LTBI) effectively prevents its progression to active TB. However, long treatment duration and drug-related hepatotoxicity limit the effectiveness of the 9-month daily isoniazid (9H). Data on the 3-month weekly rifapentine plus isoniazid (3 HP) in Asian populations are currently unavailable. Read More

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http://dx.doi.org/10.1016/j.tube.2018.05.013DOI Listing
July 2018
22 Reads

Isoniazid-induced hepatotoxicity and neurotoxicity in rats investigated by H NMR based metabolomics approach.

Toxicol Lett 2018 Oct 21;295:256-269. Epub 2018 Jun 21.

Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing 210094, PR China. Electronic address:

Isoniazid (INH) is a well-known therapeutic and preventive agent against tuberculosis. However, high rates of side effects with various symptoms concerning hepatotoxicity and neurotoxicity have been reported, hindering its wide and safe application in clinic. In this investigation, rats were intoxicated with INH by gavage at doses of 200 and 400 mg/kg for 7 consecutive days to develop a rat model of acute INH-induced toxicity, which was investigated by a H NMR-based metabolomics complemented with clinical assays, histopathological inspection and western blotting. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.05.032DOI Listing
October 2018
13 Reads

Three months of rifapentine and isoniazid for latent tuberculosis infection in hemodialysis patients: High rates of adverse events.

J Microbiol Immunol Infect 2019 Feb 2;52(1):158-162. Epub 2018 Jun 2.

Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan. Electronic address:

The consequences of once-weekly rifapentine plus isoniazid for 3 months (3HP) against latent tuberculosis infections in hemodialysis patients have not been studied before. This is the first study to evaluate the safety and tolerability of 3HP in this population and revealed a completion rate of 65.4%. Read More

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http://dx.doi.org/10.1016/j.jmii.2018.05.003DOI Listing
February 2019
1 Read

Hepatoprotective effect of lawsone on rifampicin-isoniazid induced hepatotoxicity in in vitro and in vivo models.

Environ Toxicol Pharmacol 2018 Jul 15;61:87-94. Epub 2018 May 15.

Addiriyah Chair for Environmental Studies, College of Science, King Saud University, P.O Box 2455, Riyadh 11451, Saudi Arabia. Electronic address:

The Drug-induced liver injury is one of the common unfavourable impacts, which seriously affects any drug therapy. This study documented the hepatoprotective efficacy of lawsone, the major bioactive naphthoquinone present in Lawsonia inermis L. (Lythraceae) using in vitro and in vivo models. Read More

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http://dx.doi.org/10.1016/j.etap.2018.05.006DOI Listing
July 2018
10 Reads
1.862 Impact Factor

Case Report of Isoniazid-Related Acute Liver Failure Requiring Liver Transplantation.

Diseases 2018 May 19;6(2). Epub 2018 May 19.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.

The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4⁻4.8%. Read More

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http://dx.doi.org/10.3390/diseases6020040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023516PMC
May 2018
3 Reads

Hot aqueous leaf extract of Lasianthera africana (Icacinaceae) attenuates rifampicin-isoniazid-induced hepatotoxicity.

J Integr Med 2018 07 8;16(4):263-272. Epub 2018 May 8.

Histopathology Laboratory, Braithwaite Memorial Specialist Hospital, 50001 Rivers State, Nigeria; Medical Laboratory Science Department, Faculty of Science, Rivers State University of Science and Technology, Nkpoku Oroworukwo, Port Harcourt, PMB 5080 Rivers State, Nigeria.

Objectives: The aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana (Icacinaceae) against isoniazid (INH) and rifampicin (RIF)-induced liver damage in rats.

Methods: The hepatoprotective effects of hot aqueous L. africana (HALA) leaf extract (0. Read More

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http://dx.doi.org/10.1016/j.joim.2018.05.001DOI Listing
July 2018
3 Reads

High-throughput toxicity testing of chemicals and mixtures in organotypic multi-cellular cultures of primary human hepatic cells.

Toxicol In Vitro 2018 Sep 8;51:83-94. Epub 2018 May 8.

Department of Chemical Engineering, Virginia Tech, Suite 245 Goodwin Hall, 635 Prices Fork Road, Blacksburg, VA 24061, USA; ICTAS Center for Systems Biology of Engineered Tissue, Virginia Tech, 333 Kelly Hall, 325 Stanger Street, Blacksburg, VA 24061, USA; School of Biomedical Engineering and Sciences, Virginia Tech, 333 Kelly Hall, 325 Stanger Street, Blacksburg, VA 24061, USA. Electronic address:

High-throughput screening (HTS) of liver toxicants can bridge the gap in understanding adverse effects of chemicals on humans. Toxicity testing of mixtures is time consuming and expensive, since the number of possible combinations increases exponentially with the number of chemicals. The combination of organotypic culture models (OCMs) and HTS assays can lead to the rapidly evaluation of chemical toxicity in a cost and time-effective manner while prioritizing chemicals that warrant additional investigation. Read More

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http://dx.doi.org/10.1016/j.tiv.2018.05.006DOI Listing
September 2018
6 Reads

Mortality from adverse drug reaction-related hospitalizations in south-west Ethiopia: A cross-sectional study.

J Clin Pharm Ther 2018 Dec 2;43(6):790-798. Epub 2018 May 2.

Division of Pharmacy, School of Medicine, University of Tasmania, Hobart, TAS, Australia.

What Is Known And Objective: Adverse drug reactions (ADRs) are an important cause of mortality during medical care. To our knowledge, no Ethiopian studies have reported on mortality due to ADRs in patients presenting to hospital from the community setting. The aim of this study was to determine the mortality rate attributable to ADRs in patients presenting to hospital, identify drugs implicated in the ADR-related deaths and identify factors contributing to ADR-related mortality at Jimma University Specialised Hospital (JUSH), south-west Ethiopia METHODS: This cross-sectional study included 1001 patients aged ≥18 years consecutively admitted to medical wards from May 2015 to August 2016. Read More

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http://doi.wiley.com/10.1111/jcpt.12702
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http://dx.doi.org/10.1111/jcpt.12702DOI Listing
December 2018
6 Reads

Hepatoprotective Evaluation of against Drug-induced Hepatotoxicity of Antitubercular Agents in Rats.

Pharmacogn Mag 2018 Apr-Jun;14(54):180-185. Epub 2018 Apr 10.

Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, Uttar Pradesh, India.

Background: Medicinal herbs are significantly effective against a variety of liver disorders and was traditionally used for the treatment of anti-inflammatory, pain disorder, and various types of hepatic ailment.

Objective: The purpose of this study was to evaluate the hepatoprotective activity of fruit peel extract against antitubercular drugs (isoniazid + rifampicin [INH + RIF])-induced hepatotoxicity in rats.

Materials And Methods: Liver toxicity was induced by INH + RIF at a dose level of 50 mg/kg each, intraperitoneally. Read More

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http://dx.doi.org/10.4103/pm.pm_237_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909312PMC
April 2018
3 Reads

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

Euro Surveill 2018 Apr;23(14)

National Health and Medical Research Council, NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Read More

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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.14.17-00543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894253PMC
April 2018
9 Reads

Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

BMC Med 2018 03 28;16(1):46. Epub 2018 Mar 28.

University of St Andrews Medical School, St Andrews, UK.

Background: Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment.

Methods: Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Read More

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http://dx.doi.org/10.1186/s12916-018-1033-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875008PMC
March 2018
11 Reads

A systematic review of adverse events of rifapentine and isoniazid compared to other treatments for latent tuberculosis infection.

Pharmacoepidemiol Drug Saf 2018 Jun 23;27(6):557-566. Epub 2018 Mar 23.

Ottawa Hospital, Ottawa, Canada.

Purpose: Tuberculosis (TB) remains a common cause of death globally. A regimen of 12 doses of isoniazid (INH) and rifapentine given once weekly (INH/RPT-3) has recently been recommended by the World Health Organization for the treatment of latent TB infection (LTBI). We aimed to determine whether the INH/RPT-3 regimen had similar or lesser rates of adverse events compared to other LTBI regimens, namely INH for 9 months, INH for 6 months, rifampin for 3 to 4 months, and rifampin plus INH for 3 to 4 months. Read More

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http://dx.doi.org/10.1002/pds.4423DOI Listing
June 2018
12 Reads

Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity.

Front Pharmacol 2018 7;9:198. Epub 2018 Mar 7.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.

Tuberculosis (TB) is one of the oldest infectious diseases that affected humankind and remains one of the world's deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH) in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS) potentially enhanced INH toxicity. Read More

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http://dx.doi.org/10.3389/fphar.2018.00198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850051PMC
March 2018
5 Reads

Isoniazid induces apoptosis: Role of oxidative stress and inhibition of nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2).

Life Sci 2018 Apr 27;199:23-33. Epub 2018 Feb 27.

PCS 103 Genotoxicity Lab, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address:

Aims: Long-term treatment of Isoniazid (INH) in tuberculosis (TB) patients can lead to anti-tuberculosis drug-induced hepatotoxicity. To understand the mechanism of hepatotoxicity, an attempt has been made to elucidate the role of Nrf2, a transcription factor induced by oxidative stress, in INH induced apoptosis liver cancer cell lines.

Materials And Methods: Cytotoxicity was evaluated by MTT assay. Read More

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http://dx.doi.org/10.1016/j.lfs.2018.02.037DOI Listing
April 2018
8 Reads
2.702 Impact Factor

Phenolic acid-tethered isoniazid for abrogation of drug-induced hepatotoxicity: design, synthesis, kinetics and pharmacological evaluation.

Drug Deliv Transl Res 2018 Jun;8(3):770-779

Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth University, Erandwane, Pune, Maharashtra, 411038, India.

Morphological and metabolic aberrations in the liver caused by long-term use of anti-tubercular agent isoniazid (INH) have been an issue of great concern in tuberculosis treatment. To resolve this issue, a novel hepatoprotective prodrug strategy was developed by combining the antioxidant property of phenolic acids with INH moiety for probable synergistic effect. In this work, INH was conjugated with phenolic antioxidants using Schotten-Baumann reaction through biocleavable amide linkage. Read More

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http://dx.doi.org/10.1007/s13346-018-0500-1DOI Listing
June 2018
3 Reads

Latent tuberculosis in childhood: tolerability of two different therapeutic approaches.

Expert Rev Anti Infect Ther 2018 04 21;16(4):359-365. Epub 2018 Feb 21.

a Department of Health Sciences , University of Florence, Anna Meyer Children's University Hospital , Florence , Italy.

Background: Isoniazid monotherapy for six or nine months and the combination of isoniazid and rifampicin for three or four months are the most used regimens for treating latent tuberculosis. The main aim of this retrospective study is to evaluate the safety of latent tuberculosis treatment by analysing side effects in both regimens.

Research Design And Methods: Children with latent tuberculosis and treated with isoniazid or isoniazid and rifampicin were included. Read More

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http://dx.doi.org/10.1080/14787210.2018.1441025DOI Listing
April 2018
7 Reads

First-line anti-tuberculosis drugs induce hepatotoxicity: A novel mechanism based on a urinary metabolomics platform.

Biochem Biophys Res Commun 2018 03 15;497(2):485-491. Epub 2018 Feb 15.

Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; College of Pharmaceutical Sciences, Soochow University, Suzhou 215006, China. Electronic address:

Tuberculosis (TB) has become a global public health and social threat. As clinical first-line drugs, rifampicin and isoniazid used in combination with pyrazinamide and ethambutol (the HRZE regimen) usually induce hepatotoxicity. However, the mechanisms underlying this phenomenon remain unclear, and studying the metabolic impact of co-treating TB patients with the HRZE regimen can provide new hepatotoxicity evidence. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0006291X183025
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http://dx.doi.org/10.1016/j.bbrc.2018.02.030DOI Listing
March 2018
12 Reads

New hydrazides derivatives of isoniazid against Mycobacterium tuberculosis: Higher potency and lower hepatocytotoxicity.

Eur J Med Chem 2018 Feb 31;146:529-540. Epub 2018 Jan 31.

Fundacao Oswaldo Cruz, Instituto de Tecnologia em Fármacos, Farmanguinhos-Fiocruz, Departamento de Sintese Farmacos, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil. Electronic address:

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.01.071DOI Listing
February 2018
10 Reads

Hepatotoxicity During Isoniazid Preventive Therapy and Antiretroviral Therapy in People Living With HIV With Severe Immunosuppression: A Secondary Analysis of a Multi-Country Open-Label Randomized Controlled Clinical Trial.

J Acquir Immune Defic Syndr 2018 May;78(1):54-61

UNC-Project Malawi, Lilongwe, Malawi.

Background: Hepatotoxicity associated with isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) has not been well studied in severely immunosuppressed people with HIV. Our objective was to determine risk factors for hepatotoxicity in severely immunosuppressed individuals taking IPT and ART.

Setting: Multicenter study in resource-limited settings with high burden of tuberculosis. Read More

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http://dx.doi.org/10.1097/QAI.0000000000001641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889344PMC
May 2018
12 Reads

Completion Rate and Safety of Tuberculosis Infection Treatment With Shorter Regimens.

Pediatrics 2018 02;141(2)

Department of Pediatrics, Baylor College of Medicine, Houston, Texas.

Background: The traditional treatment of tuberculosis (TB) infection (9 months of daily isoniazid [9H]) is safe but completion rates of <50% are reported. Shorter regimens (3 months of once-weekly isoniazid and rifapentine [3HP] or 4 months of daily rifampin [4R]) are associated with improved adherence in adults.

Methods: This was a retrospective cohort study (2014-2017) of children (0-18 years old) seen at a children's TB clinic in a low-incidence nation. Read More

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http://pediatrics.aappublications.org/lookup/doi/10.1542/ped
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http://dx.doi.org/10.1542/peds.2017-2838DOI Listing
February 2018
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Treatment of Latent Tuberculosis Infection and Its Clinical Efficacy.

Tuberc Respir Dis (Seoul) 2018 Jan;81(1):6-12

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea.

The role of the treatment for latent tuberculosis infection (LTBI) has been underscored in the intermediate tuberculosis (TB) burden countries like South Korea. LTBI treatment is recommended only for patients at risk for progression to active TB-those with frequent exposure to active TB cases, and those with clinical risk factors (e.g. Read More

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http://dx.doi.org/10.4046/trd.2017.0052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771748PMC
January 2018
4 Reads

Protective effects of salep against isoniazid liver toxicity in wistar rats.

J Tradit Complement Med 2018 Jan 21;8(1):239-243. Epub 2017 Jun 21.

Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran.

Introduction: Isoniazid is a drug for treatment of tuberculosis. One of the main side effects of this drug is hepatotoxicity, which is a major cause of treatment interruption in tuberculosis. This study is about the preventive effect of Salep on this side effect of isoniazid. Read More

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http://dx.doi.org/10.1016/j.jtcme.2017.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756020PMC
January 2018
5 Reads

A Randomized, Controlled, Phase III Clinical Trial to Evaluate the Efficacy and Tolerability of Risorine with Conventional Rifampicin in the Treatment of Newly Diagnosed Pulmonary Tuberculosis Patients.

J Assoc Physicians India 2017 Sep;65(9):48-54

Associate Professor, Department of TB and Chest, GMERS Medical College, Vadodara, Gujarat.

Background: The overall goals for treatment of Tuberculosis (TB) are to cure individual patient and to minimize the transmission of Mycobacterium tuberculosis. At the time of study conduction, the standard treatment for newly diagnosed tuberculosis patients consisted of an intensive phase for two months with four drugs (HRZE), followed by continuation phase for four months with two drugs (HR). Rifampicin, which is very effective against Mycobacterium tuberculosis, in both the phases of treatment, has certain concerns, which includes, decreased bioavailability with chronic use and hepatotoxicity. Read More

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September 2017
4 Reads

SIRCLE: a randomised controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication.

Intern Med J 2017 12;47(12):1433-1436

Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Background: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. Read More

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http://dx.doi.org/10.1111/imj.13601DOI Listing
December 2017
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The susceptibility of anti-tuberculosis drug-induced liver injury and chronic hepatitis C infection: A systematic review and meta-analysis.

J Chin Med Assoc 2018 02 6;81(2):111-118. Epub 2017 Dec 6.

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.

Background: Anti-tuberculosis drug-induced liver injury (ATDILI) is a major safety concern in the treatment of tuberculosis (TB). The impact of chronic hepatitis C (CHC) infection on the risk of ATDILI is still controversial. We aimed to assess the influence of CHC infection on ATDILI through a systematic review and meta-analysis. Read More

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http://dx.doi.org/10.1016/j.jcma.2017.10.002DOI Listing
February 2018
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Association between effectiveness of tuberculosis treatment and cytochrome P-4502E1 polymorphism of the patients.

Int J Mycobacteriol 2017 Oct-Dec;6(4):396-400

Department of Internal Medicine, Kharkiv National Medical University; Department of Internal Medicine, V. N. Karazin Kharkiv National University, Kharkiv, Ukraine.

Context: The risk of antituberculosis (TB) drug-induced liver injury could be determined by patients' genotype polymorphism of the xenobiotic-metabolizing enzymes. To find the meaning of cytochrome P-4502E1 (CYP2E1) polymorphism in TB patients. Corresponding of CYP2E1 polymorphism in TB patients with the level of isoniazid and rifampicin as well as for the outcome and toxicity development during inpatient TB treatment. Read More

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http://dx.doi.org/10.4103/ijmy.ijmy_168_17DOI Listing
September 2018
5 Reads

Assessment of hepatotoxicity of first-line anti-tuberculosis drugs on Wistar rats.

Naunyn Schmiedebergs Arch Pharmacol 2018 01 9;391(1):83-93. Epub 2017 Nov 9.

Cytogenetics Laboratory, Department of Zoology, Panjab University, Chandigarh, 160014, India.

Adverse drug reactions are inevitable risk factors associated with use of modern medicines. First-line anti-tuberculosis drugs contribute to diverse pathological complications, and hepatotoxicity is one of them. This study investigated the effects of anti-TB drugs in combination (rifampicin [RIF] + isoniazid [INH] + pyrazinamide [PZA]) on Wistar rats. Read More

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http://dx.doi.org/10.1007/s00210-017-1434-8DOI Listing
January 2018
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Impairment of Mitochondrial Biogenesis and Dynamics Involved in Isoniazid-Induced Apoptosis of HepG2 Cells Was Alleviated by p38 MAPK Pathway.

Front Pharmacol 2017 26;8:753. Epub 2017 Oct 26.

Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, PLA, Beijing, China.

Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. Read More

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http://dx.doi.org/10.3389/fphar.2017.00753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662931PMC
October 2017
20 Reads

Investigations on the Influence of Zidovudine in the Pharmacokinetics of Isoniazid and Its Hepatotoxic Metabolites in Rats.

J Pharm Pract 2017 Jan 1:897190017735424. Epub 2017 Jan 1.

1 Food and Hepatotoxicology Laboratory, Department of Pharmacology and Environmental Toxicology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.

The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites. Read More

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http://dx.doi.org/10.1177/0897190017735424DOI Listing
January 2017
7 Reads

Effect of goat milk on hepatotoxicity induced by antitubercular drugs in rats.

J Food Drug Anal 2016 10 2;24(4):716-721. Epub 2016 Jun 2.

Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.

Aim of the present study was to assess the hepatoprotective activity of goat milk on antitubercular drug-induced hepatotoxicity in rats. Hepatotoxicity was induced in rats using a combination of isoniazid, rifampicin, and pyrazinamide given orally as a suspension for 30 days. Treatment groups received goat milk along with antitubercular drugs. Read More

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http://dx.doi.org/10.1016/j.jfda.2016.03.012DOI Listing
October 2016
5 Reads
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0.400 Impact Factor

Deficiency of N-acetyltransferase increases the interactions of isoniazid with endobiotics in mouse liver.

Biochem Pharmacol 2017 12 6;145:218-225. Epub 2017 Sep 6.

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address:

Acetylation is the major metabolic pathway of isoniazid (INH) mediated by N-acetyltransferases (NATs). Previous reports suggest that slow acetylators have higher risks of INH hepatotoxicity than rapid acetylators, but the detailed mechanisms remain elusive. The current study used Nat1/2(-/-) mice to mimic NAT slow metabolizers and to investigate INH metabolism in the liver. Read More

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http://dx.doi.org/10.1016/j.bcp.2017.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681379PMC
December 2017
76 Reads

Drug-Induced Liver Injury in Children: Clinical Observations, Animal Models, and Regulatory Status.

Int J Toxicol 2017 Sep/Oct;36(5):365-379. Epub 2017 Aug 18.

4 Gen-X-Tox, LLC, Sarasota, FL, USA.

Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. Read More

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http://dx.doi.org/10.1177/1091581817721675DOI Listing
June 2018
29 Reads

Treatment of Latent Tuberculosis Infection: An Updated Network Meta-analysis.

Ann Intern Med 2017 Aug 1;167(4):248-255. Epub 2017 Aug 1.

From Institute for Global Health, University College London; Public Health England; and Royal Free London National Health Service Foundation Trust, London, United Kingdom, and European Centre for Disease Prevention and Control, Stockholm, Sweden.

Background: Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI.

Purpose: To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children.

Data Sources: PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. Read More

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http://dx.doi.org/10.7326/M17-0609DOI Listing
August 2017
47 Reads