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isoniazid AND pharmacokinetics

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Laure Lalande, Laurent Bourguignon, Pascal Maire, Sylvain Goutelle
Tuberculosis (TB) treatment needs to be optimized as it is currently long and associated with increasing drug resistance. The antimycobacterial effect of isoniazid (INH) is characterized by a biphasic kill curve, whose causes are still debated. In this work, we developed a complete mathematical model describing the time-course of TB infection and its treatment by INH in human lung. This model was based on a pharmacokinetic model, a pharmacodynamic model and a pathophysiological model. It was used to simulate the antibacterial effect of INH during the first days of therapy...
June 21, 2016: Journal of Theoretical Biology
Thomas Pouplin, Nguyen Duc Bang, Pham Van Toi, Pham Nguyen Phuong, Nguyen Huy Dung, Tran Ngoc Duong, Maxine Caws, Guy E Thwaites, Joel Tarning, Jeremy N Day
BACKGROUND: Among the various forms of TB, tuberculous meningitis (TBM) is the most severe, with about 30% mortality and 50% of survivors left with neurological sequelae. Children suffer more frequently from TBM than adults and outcomes are often poor due to difficulties in making the diagnosis and uncertainty regarding the best anti-tuberculosis drug regimen. The aim of this prospective study was to describe the pharmacokinetics of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of children with tuberculous meningitis treated with the standard TBM regimen...
2016: BMC Infectious Diseases
Sh A Shomurotov, G Mamadullaev, A S Turaev
The polymeric anti-tubercular drug systems "Biophthizoetham-K" and "Biophthizoetham-P" have been obtained by chemical modification of parent compounds isoniazid and ethambutol with carboxymethilcellulose and polygalacturonic acid. These systems were less toxic then the parent compounds; they exhibited prolonged anti-tubercular action at a dose sixfold lower than isoniazid. Pharmacokinetic studies have shown that after administration of "Biophthizoetham-K" and "Biophthizoetham-P", therapeutic concentration of active substances (isoniazid and ethambutol) in blood remained longer than after administration of active substances alone...
January 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
Noton K Dutta, Natalie Bruiners, Michael L Pinn, Matthew D Zimmerman, Brendan Prideaux, Véronique Dartois, Maria L Gennaro, Petros C Karakousis
BACKGROUND: The repurposing of existing agents may accelerate TB drug development. Recently, we reported that the lipid-lowering drug simvastatin, when added to the first-line antitubercular regimen, reduces the lung bacillary burden in chronically infected mice. OBJECTIVES: We investigated whether the addition of simvastatin to the first-line regimen (isoniazid/rifampicin/pyrazinamide) shortens the duration of curative TB treatment in mice. METHODS: Mycobacterium tuberculosis-infected THP-1 cells were exposed to simvastatin to determine the effect of statins on the activity of first-line anti-TB drug activity and intracellular rifampicin concentration...
June 2016: Journal of Antimicrobial Chemotherapy
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