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isoniazid AND pharmacokinetics

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https://www.readbyqxmd.com/read/28862186/food-significantly-reduces-plasma-concentrations-of-first-line-anti-tuberculosis-drugs
#1
Agibothu Kupparam Hemanth Kumar, Vedachalam Chandrasekaran, Angadi Kiran Kumar, M Kawaskar, J Lavanya, Soumya Swaminathan, Geetha Ramachandran
BACKGROUND & OBJECTIVES: Concomitant feeding and anti-tuberculosis (TB) drug administration are likely to reduce nausea and enhance compliance to treatment. However, food could lower plasma drug concentrations. This study was undertaken to examine the effect of food on two-hour plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA), and pharmacokinetics of these drugs in adult TB patients. METHODS: Newly diagnosed adult TB patients were recruited from the Revised National Tuberculosis Control Programme (RNTCP) treatment centres in Chennai Corporation, Chennai, India...
April 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28835350/development-of-water-soluble-3-5-dinitrophenyl-tetrazole-and-oxadiazole-antitubercular-agents
#2
Jaroslav Roh, Galina Karabanovich, Hana Vlčková, Alejandro Carazo, Jan Němeček, Pavel Sychra, Lenka Valášková, Oto Pavliš, Jiřina Stolaříková, Věra Klimešová, Kateřina Vávrová, Petr Pávek, Alexandr Hrabálek
In this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N-benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against Mycobacterium tuberculosis CNCTC My 331/88 (H37Rv), comparable to those of the first-line drugs isoniazid and rifampicin...
August 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28827417/pharmacokinetics-tolerability-and-bacteriological-response-of-600-900-and-1200-mg-rifampicin-daily-in-patients-with-pulmonary-tb
#3
R E Aarnoutse, G S Kibiki, K Reither, H H Semvua, F Haraka, C M Mtabho, S G Mpagama, J van den Boogaard, I M Sumari-de Boer, C Magis-Escurra, M Wattenberg, J G M Logger, L H M Te Brake, M Hoelscher, S H Gillespie, A Colbers, P P J Phillips, G Plemper van Balen, M J Boeree
Background. In a multiple dose ranging trial we have previously evaluated higher doses of rifampicin in patients for two weeks. The objectives of the current study were to administer higher doses of rifampicin for a longer period to compare pharmacokinetics, safety/tolerability and bacteriological activity of such regimens.Methods. In a double-blinded, randomized, placebo-controlled, phase II clinical trial (ClinicalTrials.gov NCT00760149) 150 Tanzanian TB patients were randomized to receive either 600 (approximately 10 mg/kg), 900 or 1200 mg rifampicin combined with standard doses of isoniazid, pyrazinamide and ethambutol administered daily for two months...
August 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28741299/a-review-of-moxifloxacin-for-the-treatment-of-drug-susceptible-tuberculosis
#4
REVIEW
Anushka Naidoo, Kogieleum Naidoo, Helen McIlleron, Sabiha Essack, Nesri Padayatchi
Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance...
July 24, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28719501/evaluation-of-the-adequacy-of-the-2010-revised-world-health-organization-recommended-dosages-of-the-first-line-antituberculosis-drugs-for-children
#5
Hongmei Yang, Anthony Enimil, Fizza S Gillani, Sampson Antwi, Albert Dompreh, Antoinette Ortsin, Eugene Adu Awhireng, Maxwell Owusu, Lubbe Wiesner, Charles A Peloquin, Awewura Kwara
BACKGROUND: The World Health Organization recommended increased dosages of the first-line antituberculosis (anti-TB) drugs for children in 2010. We examined the frequency of and factors associated with low plasma maximum concentration (Cmax) of each drug in children treated with the revised dosages. METHODS: Children on anti-TB therapy for at least 4 weeks underwent pharmacokinetic testing. Plasma Cmax below the lower limit of proposed reference range was considered low...
July 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28657202/assessing-pharmacodynamic-interactions-in-mice-using-the-multistate-tuberculosis-pharmacometric-and-general-pharmacodynamic-interaction-models
#6
Chunli Chen, Sebastian G Wicha, Gerjo J de Knegt, Fatima Ortega, Laura Alameda, Veronica Sousa, Jurriaan E M de Steenwinkel, Ulrika S H Simonsson
The aim of this study was to investigate pharmacodynamic interactions in mice infected with Mycobacterium tuberculosis using population pharmacokinetics, the Multistate Tuberculosis Pharmacometric (MTP) model, and the General Pharmacodynamic Interaction (GPDI) model. Rifampicin, isoniazid, ethambutol or pyrazinamide were administered in monotherapy for 4 weeks. Rifampicin and isoniazid showed effects in monotherapy, whereas the animals became moribund after 7 days with ethambutol or pyrazinamide alone. No pharmacodynamic interactions were observed against fast-multiplying bacteria...
June 28, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28653479/a-population-pharmacokinetic-model-incorporating-saturable-pharmacokinetics-and-autoinduction-for-high-rifampicin-doses
#7
Robin J Svensson, Rob E Aarnoutse, Andreas H Diacon, Rodney Dawson, Stephen H Gillespie, Martin J Boeree, Ulrika S H Simonsson
Accumulating evidence suggests that increasing doses of rifampicin may shorten tuberculosis treatment. The PanACEA HIGHRIF1 trial assessed safety, pharmacokinetics, and antimycobacterial activity of rifampicin at doses up to 40 mg/kg. Eighty-three pulmonary tuberculosis patients received 10, 20, 25, 30, 35, or 40 mg/kg rifampicin daily over 2 weeks, supplemented with standard doses of isoniazid, pyrazinamide, and ethambutol in the second week. This study aimed at characterizing rifampicin pharmacokinetics observed in HIGHRIF1 using nonlinear mixed effects modeling...
June 27, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-and-optimal-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#8
Maxwell T Chirehwa, Helen McIlleron, Roxana Rustomjee, Thuli Mthiyane, Philip Onyebujoh, Peter Smith, Paolo Denti
Pyrazinamide is used in the treatment of tuberculosis (TB) because its sterilizing effect against tubercle bacilli allows the shortening of treatment. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multidrug-resistant tuberculosis (MDR-TB)...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28506804/chloroquine-enhances-the-antimycobacterial-activity-of-isoniazid-and-pyrazinamide-by-reversing-inflammation-induced-macrophage-efflux
#9
U Matt, P Selchow, M Dal Molin, S Strommer, O Sharif, K Schilcher, F Andreoni, A Stenzinger, A S Zinkernagel, M Zeitlinger, P Sander, J Nemeth
Mycobacterium tuberculosis (MTB) is notorious for persisting within host macrophages. Efflux pumps decrease intracellular drug levels, thus fostering persistence of MTB during therapy. Isoniazid (INH) and pyrazinamide (PZA) are substrates of the efflux pump breast cancer resistance protein-1 (BCRP-1), which is inhibited by chloroquine (CQ). In this study, BCRP-1 was found to be expressed on macrophages of human origin and on foamy giant cells at the site of MTB infection. In the current in vitro study, interferon-gamma (IFNγ) increased the expression of BCRP-1 in macrophages derived from the human monocytic leukaemia cell line THP-1...
May 12, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28495479/limited-sampling-strategies-for-determining-the-area-under-the-plasma-concentration-time-curve-for-isoniazid-might-be-a-valuable-approach-for-optimizing-treatment-in-adult-patients-with-tuberculosis
#10
Piergiorgio Cojutti, Manuela Giangreco, Miriam Isola, Federico Pea
This study aimed to develop clinically feasible models of limited sampling strategy (LSS) for estimation of the area under the concentration-time curve (AUC24h) for isoniazid, that could be applied easily in daily clinical practice for dosage adjustment in adult patients with tuberculosis. Isoniazid plasma concentrations (n = 1665) from 185 adult tuberculous patients were used for the development and validation of LSS models to estimate AUC24h following administration of the standard 5 mg/kg dose of isoniazid...
July 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28419277/prevention-of-tb-using-rifampicin-plus-isoniazid-reduces-nevirapine-concentrations-in-hiv-exposed-infants
#11
Helen McIlleron, Paolo Denti, Silvia Cohn, Fildah Mashabela, Jennifer D Hoffmann, Saba Shembe, Regina Msandiwa, Lubbe Wiesner, Sithembiso Velaphi, Sanjay G Lala, Richard E Chaisson, Neil Martinson, Kelly E Dooley
Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis...
July 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333192/susceptibilities-of-mdr-mycobacterium-tuberculosis-isolates-to-unconventional-drugs-compared-with-their-reported-pharmacokinetic-pharmacodynamic-parameters
#12
Joseph S Cavanaugh, Ruwen Jou, Mei-Hua Wu, Tracy Dalton, Ekaterina Kurbatova, Julia Ershova, J Peter Cegielski
Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28160272/suboptimal-exposure-to-anti-tb-drugs-in-a-tbm-hiv-population-is-not-related-to-anti-retroviral-therapy
#13
M E Török, G Aljayyoussi, D Waterhouse, Tth Chau, Nth Mai, N H Phu, T T Hien, W Hope, J J Farrar, S A Ward
A placebo-controlled trial that compares the outcomes of immediate versus deferred initiation of antiretroviral therapy in HIV+ve Tuberculous Meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of Rifampicin, Isoniazid, Pyrazinamide and Ethambutol were investigated in the presence and absence of anti-HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact upon the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low CSF and systemic exposures to rifampicin compared to previously reported HIV -ve cohorts...
February 4, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28157477/pharmacokinetics-and-pharmacodynamics-of-isoniazid-in-patients-with-intermediate-resistance
#14
Abdullah Alsultan, Charles A Peloquin
No abstract text is available yet for this article.
January 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/27855070/pharmacokinetics-of-the-first-line-antituberculosis-drugs-in-ghanaian-children-with-tuberculosis-with-or-without-hiv-coinfection
#15
Sampson Antwi, Hongmei Yang, Anthony Enimil, Anima M Sarfo, Fizza S Gillani, Daniel Ansong, Albert Dompreh, Antoinette Orstin, Theresa Opoku, Dennis Bosomtwe, Lubbe Wiesner, Jennifer Norman, Charles A Peloquin, Awewura Kwara
Although human immunodeficiency virus (HIV) coinfection is the most important risk factor for a 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 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 predose and at 1, 2, 4, and 8 hours postdose...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27792837/isoniazid-clearance-is-impaired-among-human-immunodeficiency-virus-tuberculosis-patients-with-high-levels-of-immune-activation
#16
Christopher Vinnard, Shruthi Ravimohan, Neo Tamuhla, Vijay Ivaturi, Jotam Pasipanodya, Shashikant Srivastava, Chawangwa 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 antiretroviral therapy (ART) would be associated with impaired clearance of isoniazid. METHODS: We conducted a prospective observational study of isoniazid pharmacokinetics (PK) and systemic immune activation prior to and 1 month after ART initiation...
April 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27780145/circadian-variation-of-isoniazid-pharmacokinetics-in-mice
#17
COMPARATIVE STUDY
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...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27775177/recent-advances-and-structural-features-of-enoyl-acp-reductase-inhibitors-of-mycobacterium-tuberculosis
#18
REVIEW
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)...
November 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
#19
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
#20
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
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