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isoniazid AND pharmacokinetics

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https://www.readbyqxmd.com/read/27855070/pharmacokinetics-of-the-first-line-antituberculosis-drugs-in-ghanaian-children-with-tuberculosis-with-and-without-hiv-coinfection
#1
Sampson Antwi, Hongmei Yang, Anthony Enimil, Anima M Sarfo, Fizza S Gillani, Daniel Ansong, Albert Dompreh, Antoinette Orstin, Theresa Opoku, Dennis Bosumtwe, Lubbe Wiesner, Jennifer Norman, Charles A Peloquin, Awewura Kwara
Although human immunodefiency virus (HIV) coinfection is the most important risk factor for poor antituberculosis (anti-TB) treatment response, its effect on the pharmacokinetics of the first-line drugs in children is understudied. This study examined the pharmacokinetics of the four first-line anti-TB drugs in children with tuberculosis (TB) with and without HIV coinfection. Ghanaian children with TB on isoniazid, rifampin, pyrazinamide and ethambutol for at least 4 weeks had blood samples collected at pre-dose, 1, 2, 4, and 8-hours post-dose...
November 14, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27792837/isoniazid-clearance-is-impaired-among-hiv-tuberculosis-patients-with-high-levels-of-immune-activation
#2
Christopher Vinnard, Shruthi Ravimohan, Neo Tamuhla, Vijay Ivaturi, Jotam Pasipanodya, Shashikant Srivastava, Chawa Modongo, Nicola M Zetola, Drew Weissman, Tawanda Gumbo, Gregory P Bisson
AIMS: Immune activation, which is characteristic of both tuberculosis (TB) and human immunodeficiency virus (HIV) infection, is associated with impaired drug metabolism. We tested the hypothesis that elevated levels of systemic immune activation among adults with HIV/TB initiating ART would be associated with impaired clearance of isoniazid. METHODS: We conducted a prospective observational study of isoniazid pharmacokinetics and systemic immune activation prior to and one month after antiretroviral therapy (ART) initiation...
October 28, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27780145/circadian-variation-of-isoniazid-pharmacokinetics-in-mice
#3
Nouha Souayed, Malek Chennoufi, Nadia Ben Frej, Amel Chaabane, Mossadok Ben-Attia, Karim Aouam, Alain Reinberg, Naceur A Boughattas
INTRODUCTION: This study is designed to investigate whether the pharmacokinetics of the antituberculous agent isoniazid (INH) varied according to the circadian dosing-time. METHODS: A total of 168 male mice aged 10 weeks and synchronized for 3 weeks to 12h light and 12h dark were used. A single INH (100mg/kg) dose was administered by intraperitonal (i.p.) route at either of the four different circadian stages (1, 7, 13 and 19h after light onset, HALO). At each circadian stage, blood samples were withdrawn at 0, 0...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27775177/recent-advances-and-structural-features-of-enoyl-acp-reductase-inhibitors-of-mycobacterium-tuberculosis
#4
Bharathkumar Inturi, Gurubasavaraj V Pujar, Madhusudhan N Purohit
Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug-resistant TB (MDR-TB)...
October 24, 2016: Archiv der Pharmazie
https://www.readbyqxmd.com/read/27742640/a-faropenem-linezolid-and-moxifloxacin-regimen-for-both-drug-susceptible-and-multidrug-resistant-tuberculosis-in-children-flame-path-on-the-milky-way
#5
Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  The regimen of linezolid and moxifloxacin was found to be efficacious in the hollow fiber system model of pediatric intracellular tuberculosis. However, its kill rate was slower than the standard 3-drug regimen of isoniazid, rifampin, and pyrazinamide. We wanted to examine the effect of adding a third oral agent, faropenem, to this dual combination. METHODS:  We performed a series of studies in the hollow fiber system model of intracellular Mycobacterium tuberculosis, by mimicking pediatric pharmacokinetics of each antibiotic...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27742636/drug-concentration-thresholds-predictive-of-therapy-failure-and-death-in-children-with-tuberculosis-bread-crumb-trails-in-random-forests
#6
Soumya Swaminathan, Jotam G Pasipanodya, Geetha Ramachandran, A K Hemanth Kumar, Shashikant Srivastava, Devyani Deshpande, Eric Nuermberger, Tawanda Gumbo
BACKGROUND:  The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. METHODS:  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27724114/the-challenges-of-pharmacokinetic-variability-of-first-line-anti-tb-drugs
#7
Bella Devaleenal D, Geetha Ramachandran, Soumya Swaminathan
Inter-individual variations in the pharmacokinetics (PK) of anti-TB drugs are known to occur, which could have important therapeutic implications in patient management. Areas covered: We compiled factors responsible for PK variability of anti-TB drugs reported from different settings that would give a better understanding about the challenges of PK variability of anti-TB medications. We searched PubMed data base and Google scholar from 1976 to the present using the key words "Pharmacokinetics", "pharmacokinetic variability", "first-line anti-TB therapy", "Rifampicin", "Isoniazid", "Ethambutol", "Pyrazinamide", "food", "nutritional status", "HIV", "diabetes", "genetic polymorphisms" and "pharmacokinetic interactions"...
October 11, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27691967/isoniazid-and-rifampin-pharmacokinetics-in-two-asian-elephants-elephas-maximus-infected-with-mycobacterium-tuberculosis
#8
Eric F Egelund, Ramiro Isaza, Abdullah Alsultan, Charles A Peloquin
This report describes the pharmacokinetic profiles of chronically administered oral isoniazid and rifampin in one adult male and one adult female Asian elephant ( Elephas maximus ) that were asymptomatically infected with Mycobacterium tuberculosis . Rifampin's half-life was reduced when compared to previous single-dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both elephants experienced delayed absorption of isoniazid and rifampin as compared to previous pharmacokinetic studies in this species...
September 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/27545595/rifapentine-for-the-treatment-of-latent-tuberculosis
#9
Eric F Egelund, Charles A Peloquin
INTRODUCTION: The goal of this article is to review the use of rifapentine in the treatment of latent tuberculosis infection (LTBI). Controlling LTBI is an important part of the global strategy to end the spread of tuberculosis. Rifapentine's potent sterilizing effect against Mycobacterium tuberculosis combined with its long half-life make it an attractive LTBI treatment option. AREAS COVERED: A systematic literature search of Pubmed using the terms 'rifapentine' and 'tuberculosis' was performed...
August 22, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27510252/pharmacokinetics-of-thrice-weekly-rifampicin-isoniazid-and-pyrazinamide-in-adult-tuberculosis-patients-in-india
#10
A K Hemanth Kumar, T Kannan, V Chandrasekaran, V Sudha, A Vijayakumar, K Ramesh, J Lavanya, S Swaminathan, G Ramachandran
OBJECTIVE: To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that influence drug pharmacokinetics. METHODS: Adult TB patients (n = 101) receiving thrice-weekly anti-tuberculosis treatment in the Revised National TB Control Programme (RNTCP) were studied. The study was conducted at steady state after directly observed drug administration. RMP, INH and PZA concentrations were estimated using high-performance liquid chromatography and NAT2 genotyping by real-time polymerase chain reaction...
September 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/27473307/population-pharmacokinetics-optimised-design-and-sample-size-determination-for-rifampicin-isoniazid-ethambutol-and-pyrazinamide-in-the-mouse
#11
Chunli Chen, Fatima Ortega, Laura Alameda, Santiago Ferrer, Ulrika S H Simonsson
The current first-line therapy for drug-susceptible tuberculosis consists of rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB). In this study, we determined the population pharmacokinetics (PopPK) of RIF, INH, EMB and PZA using original experimental sampling designs for single-dose intravenous (IV) and single- and multiple-dose oral administration studies in the mouse model, and used these PopPK models to develop and evaluate new, more informative sampling designs with the aim of reducing the number of animals required for each drug...
October 10, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27458223/delamanid-coadministered-with-antiretroviral-drugs-or-antituberculosis-drugs-shows-no-clinically-relevant-drug-drug-interactions-in-healthy-subjects
#12
Suresh Mallikaarjun, Charles Wells, Carolyn Petersen, Anne Paccaly, Susan E Shoaf, Shiva Patil, Lawrence Geiter
Delamanid is a medicinal product approved for treatment of multidrug-resistant tuberculosis. Three studies were conducted to evaluate the potential drug-drug interactions between delamanid and antiretroviral drugs, including ritonavir, a strong inhibitor of CYP3A4, and selected anti-TB drugs, including rifampin, a strong inducer of cytochrome P450 (CYP) isozymes. Multiple-dose studies were conducted in parallel groups of healthy subjects. Plasma samples were analyzed for delamanid, delamanid metabolite, and coadministered drug concentrations, and pharmacokinetic (PK) parameters were determined...
October 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27446292/ratio-of-microrna-122-155-in-isoniazid-induced-acute-liver-injury-in-mice
#13
Lei Song, Zhongrui Zhang, Jinling Zhang, Xuebin Zhu, Lei He, Zhe Shi, Li Gao, Fumin Feng
Liver injury is a major hindrance to the treatment of tuberculosis (TB) patients due to the primary side effects associated with anti-TB drugs. Several investigations have identified sensitive biomarkers for the early diagnosis of anti-TB drug-induced liver injury (ADLI), including the use of microRNAs (miRNAs/miRs). However, the association between miR-122/155 and ADLI remains unknown. Thus, the present study used reverse transcription-quantitative polymerase chain reaction to observe changes in tissue miR-122/155 expression levels during the course of liver injury in mice...
August 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27379099/pharmacologic-inhibition-of-host-phosphodiesterase-4-improves-isoniazid-mediated-clearance-of-mycobacterium-tuberculosis
#14
Selvakumar Subbian, Mi-Sun Koo, Liana Tsenova, Vikram Khetani, Jerome B Zeldis, Dorothy Fallows, Gilla Kaplan
The lengthy duration of multidrug therapy needed to cure tuberculosis (TB) poses significant challenges for global control of the disease. Moreover, chronic inflammation associated with TB leads to pulmonary damage that can remain even after successful cure. Thus, there is a great need for the development of effective shorter drug regimens to improve clinical outcome and strengthen TB control. Host-directed therapy (HDT) is emerging as a novel adjunctive strategy to enhance the efficacy and shorten the duration of TB treatment...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27305904/optimizing-treatment-outcome-of-first-line-anti-tuberculosis-drugs-the-role-of-therapeutic-drug-monitoring
#15
REVIEW
Roger K Verbeeck, Gunar Günther, Dan Kibuule, Christian Hunter, Tim W Rennie
INTRODUCTION: Tuberculosis (TB) remains one of the world's deadliest communicable diseases. Although cure rates of the standard four-drug (rifampicin, isoniazid, pyrazinamide, ethambutol) treatment schedule can be as high as 95-98 % under clinical trial conditions, success rates may be much lower in less well resourced countries. Unsuccessful treatment with these first-line anti-TB drugs may lead to the development of multidrug resistant and extensively drug resistant TB. The intrinsic interindividual variability in the pharmacokinetics (PK) of the first-line anti-TB drugs is further exacerbated by co-morbidities such as HIV infection and diabetes...
August 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27232112/pharmgkb-summary-isoniazid-pathway-pharmacokinetics
#16
Daniel J Klein, Sotiria Boukouvala, Ellen M McDonagh, Scott R Shuldiner, Nicola Laurieri, Caroline F Thorn, Russ B Altman, Teri E Klein
No abstract text is available yet for this article.
September 2016: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/27191185/quantifying-isoniazid-levels-in-small-hair-samples-a-novel-method-for-assessing-adherence-during-the-treatment-of-latent-and-active-tuberculosis
#17
Roy Gerona, Anita Wen, Aaron T Chin, Catherine A Koss, Peter Bacchetti, John Metcalfe, Monica Gandhi
BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges...
2016: PloS One
https://www.readbyqxmd.com/read/27118305/imipenem-cilastatin-induced-psychosis-a-case-report
#18
Jacob Ninan, Gemy Maria George
BACKGROUND: Elderly patients, in particular, have been reported to develop psychiatric side effects from antibiotics. Clarithromycin, quinolones, sulfamethoxazole-trimethoprim, isoniazid, penicillin, and cephalosporins have been reported to cause psychosis. This case report bridges a void in the medical literature with regards to the psychiatric adverse effects of imipenem-cilastatin. CASE PRESENTATION: A 64-year-old Hispanic man in septic shock due to urinary tract infection was initiated on imipenem-cilastatin and mechanically ventilated, following admission to hospital...
2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27095353/preparation-and-preclinical-evaluation-of-inhalable-particles-containing-rapamycin-and-anti-tuberculosis-agents-for-induction-of-autophagy
#19
Anuradha Gupta, Deepak Sharma, Jairam Meena, Sanketkumar Pandya, Madhur Sachan, Sadan Kumar, Kavita Singh, Kalyan Mitra, Sharad Sharma, Amulya K Panda, Pushpa Gupta, Umesh Datta Gupta, Amit Misra
PURPOSE: Mycobacterium tuberculosis (Mtb) inhibits host defense mechanisms, including autophagy. We investigated particles containing rapamycin (RAP) alone or in combination with isoniazid (INH) and rifabutin (RFB) for: targeting lung macrophages on inhalation; inducing autophagy; and killing macrophage-resident Mtb and/or augmenting anti-tuberculosis (TB) drugs. METHODS: PLGA and drugs were spray-dried. Pharmacokinetics, partial biodistribution (LC-MS/MS) and efficacy (colony forming units, qPCR, acid fast staining, histopathology) in mice following dry powder inhalation were evaluated...
August 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27084822/pharmacokinetics-of-isoniazid-rifampicin-pyrazinamide-and-ethambutol-in-hiv-infected-indian-children
#20
A Mukherjee, T Velpandian, M Singla, K Kanhiya, S K Kabra, R Lodha
SETTING: Co-infection with the human immunodeficiency virus (HIV) may lead to inadequate plasma concentrations of anti-tuberculosis drugs in children with tuberculosis (TB). OBJECTIVE: To describe the influence of HIV infection on the pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in children. DESIGN: Prospective drug estimation study in two cohorts of children: HIV-infected (n = 24) and non-HIV-infected (n = 32) with TB...
May 2016: International Journal of Tuberculosis and Lung Disease
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