keyword
MENU ▼
Read by QxMD icon Read
search

pharmacokinetics and TB

keyword
https://www.readbyqxmd.com/read/28928173/cohort-profile-of-a-study-on-outcomes-related-to-tuberculosis-and-antiretroviral-drug-concentrations-in-uganda-design-methods-and-patient-characteristics-of-the-south-study
#1
Christine Sekaggya-Wiltshire, Barbara Castelnuovo, Amrei von Braun, Joseph Musaazi, Daniel Muller, Allan Buzibye, Ursula Gutteck, Lars Henning, Bruno Ledergerber, Natascia Corti, Mohammed Lamorde, Jan Fehr, Andrew Kambugu
PURPOSE: Tuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes. PARTICIPANTS: Patients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on first-line anti-TB treatment...
September 18, 2017: BMJ Open
https://www.readbyqxmd.com/read/28862186/food-significantly-reduces-plasma-concentrations-of-first-line-anti-tuberculosis-drugs
#2
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/28861054/screening-of-tb-actives-for-activity-against-nontuberculous-mycobacteria-delivers-high-hit-rates
#3
Jian Liang Low, Mu-Lu Wu, Dinah Binte Aziz, Benoît Laleu, Thomas Dick
The prevalence of lung disease due to infections with nontuberculous mycobacteria (NTM) has been increasing and surpassed tuberculosis (TB) in some countries. Treatment outcomes are often unsatisfactory, highlighting an urgent need for new anti-NTM medications. Although NTM in general do not respond well to TB specific drugs, the similarities between NTM and Mycobacterium tuberculosis at the molecular and cell structural level suggest that compound libraries active against TB could be leveraged for NTM drug discovery...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28859520/the-downfall-of-tba-354-a-possible-explanation-for-its-neurotoxicity-via-mass-spectrometric-imaging
#4
Sphamandla Ntshangase, Adeola Shobo, Hendrik G Kruger, Arndt Asperger, Dagmar Niemeyer, Per I Arvidsson, Thavendran Govender, Sooraj Baijnath
TBA-354 was a promising antitubercular compound with activity against both replicating and static Mycobacterium tuberculosis (M.tb), making it the focal point of many clinical trials conducted by the TB Alliance. However, findings from these trials have shown that TBA-354 results in mild signs of reversible neurotoxicity; this left the TB Alliance with no other choice but to stop the research. In this study, mass spectrometric methods were used to evaluate the pharmacokinetics and spatial distribution of TBA-354 in the brain using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) and mass spectrometric imaging (MSI), respectively...
September 1, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28843937/determination-of-protein-unbound-active-rifampicin-in-serum-by-ultrafiltration-and-ultra-performance-liquid-chromatography-with-uv-detection-a-method-suitable-for-standard-and-high-doses-of-rifampicin
#5
Eleonora W J van Ewijk-Beneken Kolmer, Marga J A Teulen, Erik C A van den Hombergh, Nielka E van Erp, Lindsey H M Te Brake, Rob E Aarnoutse
Rifampicin is the most important antibiotic in use for the treatment of tuberculosis (TB). Preclinical and clinical data suggest that higher doses of rifampicin, resulting in disproportionally higher systemic exposures to the drug, are more effective. Serum concentrations of rifampicin are the intermediary link between the dose administered and eventual response and only protein-unbound (free) rifampicin is pharmacologically active. The objective of this work was to develop an ultra performance liquid chromatography assay for protein-unbound rifampicin in serum with ultrafiltration, carried out at a sample temperature of 37°C, suitable for measurement of concentrations achieved after currently used and higher doses of rifampicin...
August 4, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28827417/pharmacokinetics-tolerability-and-bacteriological-response-of-600-900-and-1200-mg-rifampicin-daily-in-patients-with-pulmonary-tb
#6
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/28817561/comparing-efficacies-of-moxifloxacin-levofloxacin-and-gatifloxacin-in-tuberculosis-granulomas-using-a-multi-scale-systems-pharmacology-approach
#7
Elsje Pienaar, Jansy Sarathy, Brendan Prideaux, Jillian Dietzold, Véronique Dartois, Denise E Kirschner, Jennifer J Linderman
Granulomas are complex lung lesions that are the hallmark of tuberculosis (TB). Understanding antibiotic dynamics within lung granulomas will be vital to improving and shortening the long course of TB treatment. Three fluoroquinolones (FQs) are commonly prescribed as part of multi-drug resistant TB therapy: moxifloxacin (MXF), levofloxacin (LVX) or gatifloxacin (GFX). To date, insufficient data are available to support selection of one FQ over another, or to show that these drugs are clinically equivalent. To predict the efficacy of MXF, LVX and GFX at a single granuloma level, we integrate computational modeling with experimental datasets into a single mechanistic framework, GranSim...
August 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28803492/rifampin-vs-rifapentine-what-is-the-preferred-rifamycin-for-tuberculosis
#8
Omamah Alfarisi, Wael A Alghamdi, Mohammad H Al-Shaer, Kelly E Dooley, Charles A Peloquin
One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them...
August 18, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28789609/dose-and-time-dependency-of-the-toxicity-and-pharmacokinetic-profiles-of-bedaquiline-and-its-n-desmethyl-metabolite-in-dogs
#9
Ilham Smyej, Sandra De Jonghe, Adriana Looszova, Geert Mannens, Tom Verhaeghe, Sandy Thijssen, Sofie Starckx, Ann Lampo, Marie-Claude Rouan
Bedaquiline (BDQ) is an antibiotic to treat pulmonary multidrug-resistant tuberculosis (MDR-TB). Studies up to 39 weeks were conducted orally in dogs to assess the toxicity and pharmacokinetics of BDQ and its N-desmethyl metabolite (D-BDQ). Phospholipidosis (PLD) seen in the monocytic phagocytic system was considered an adaptive change. Skeletal muscle, heart, stomach, liver, and pancreas toxicities with D-BDQ as the main contributor were associated with a less-than-dose-proportional increase in plasma exposure and an overproportional tissue uptake of BDQ and D-BDQ at high-dose levels...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28739794/population-pharmacokinetics-of-azd-5847-in-adults-with-pulmonary-tuberculosis
#10
Abdullah Alsultan, Jennifer J Furin, Jeannine Du Bois, Elana van Brakel, Phalkun Chheng, Amour Venter, Bonnie Thiel, Sara A Debanne, W Henry Boom, Andreas H Diacon, John L Johnson, Charles A Peloquin
AZD-5847 is a new oxazolidinone derivative under development for the treatment of tuberculosis. In this study we describe the population pharmacokinetics of AZD-5847 in patients with tuberculosis based on a recently completed phase II study. The study included 60 patients with drug susceptible TB. Patients were randomized to four doses (500 mg once daily, 1200 mg once daily, 500 mg twice daily and 800 mg twice daily). Patients were intensively sampled on day 1 and 14. AZD-5847 pharmacokinetics were best described with a two compartment system with tlag for absorption...
July 24, 2017: Antimicrobial Agents and Chemotherapy
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
#11
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/28715978/the-role-of-efflux-pumps-in-tuberculosis-treatment-and-their-promise-as-a-target-in-drug-development-unraveling-the-black-box
#12
Lindsey H M Te Brake, Gerjo J de Knegt, Jurriaan E de Steenwinkel, Teunis J P van Dam, David M Burger, Frans G M Russel, Reinout van Crevel, Jan B Koenderink, Rob E Aarnoutse
Insight into drug transport mechanisms is highly relevant to the efficacious treatment of tuberculosis (TB). Major problems in TB treatment are related to the transport of antituberculosis (anti-TB) drugs across human and mycobacterial membranes, affecting the concentrations of these drugs systemically and locally. Firstly, transporters located in the intestines, liver, and kidneys all determine the pharmacokinetics and pharmacodynamics of anti-TB drugs, with a high risk of drug-drug interactions in the setting of concurrent use of antimycobacterial, antiretroviral, and antidiabetic agents...
July 17, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28696241/ethambutol-partitioning-in-tuberculous-pulmonary-lesions-explains-its-clinical-efficacy
#13
Matthew Zimmerman, Jodi Lestner, Brendan Prideaux, Paul O'Brien, Isabela Dias-Freedman, Chao Chen, Jillian Dietzold, Isaac Daudelin, Firat Kaya, Landry Blanc, Pei-Yu Chen, Steven Park, Padmini Salgame, Jansy Sarathy, Véronique Dartois
Clinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against nongrowing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. Here, we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into TB lesions. First, we utilized novel in vitro lesion pharmacokinetic assays and predicted good penetration of the drug into lesions...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28623874/lansoprazole-sulfide-pharmacokinetics-of-this-promising-anti-tuberculous-agent
#14
Sipho Mdanda, Sooraj Baijnath, Adeola Shobo, Sanil D Singh, Glenn E M Maguire, Hendrik G Kruger, Per I Arvidsson, Tricia Naicker, Thavendran Govender
Lansoprazole (LPZ) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (LPZS) was recently reported to have in vitro and in vivo activity against Mycobacterium tuberculosis. It was also reported that a 300 mg kg(-1) oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates was developed...
June 17, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28609019/synthesis-biological-evaluation-and-molecular-docking-studies-of-novel-3-aryl-5-alkyl-thio-1h-1-2-4-triazoles-derivatives-targeting-mycobacterium-tuberculosis
#15
Navnath D Rode, Amol D Sonawane, Laxman Nawale, Vijay M Khedkar, Ramesh A Joshi, Anjali P Likhite, Dhiman Sarkar, Rohini R Joshi
A small library of new 3-aryl-5-(alkyl-thio)-1H-1,2,4-triazoles was synthesized and screened for the anti-mycobacterial potency against M. tuberculosis H37 Ra strain and M. bovis BCG both in active and dormant stage. Among the synthesized library, 25 compounds exhibited promising anti-TB activity in the range of IC50 0.03-5.88 μg/mL for dormant stage and 20 compounds in the range of 0.03-6.96 μg/mL for active stage. Their lower toxicity (>100 μg/mL) and higher selectivity (SI = >10) against all cancer cell lines screened makes them interesting compounds with potential anti-mycobacterial effects...
June 13, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-and-optimal-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#16
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/28584143/linezolid-dose-that-maximizes-sterilizing-effect-while-minimizing-toxicity-and-resistance-emergence-for-tuberculosis
#17
Shashikant Srivastava, Gesham Magombedze, Thearith Koeuth, Carleton Sherman, Jotam G Pasipanodya, Prithvi Raj, Edward Wakeland, Devyani Deshpande, Tawanda Gumbo
Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed linezolid dose-effect and dose-scheduling studies in the hollow fiber system model of tuberculosis (HFS-TB) for sterilizing effect. HFS-TB units were treated with several doses to mimic human-like linezolid intrapulmonary pharmacokinetics and repetitively sampled for drug concentration, total bacterial burden, linezolid-resistant subpopulations, and RNA sequencing over 2 months...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28570367/antiretroviral-dose-optimization-the-future-of-efavirenz-400%C3%A2-mg-dosing
#18
Marta Boffito, Mohammed Lamorde, Melynda Watkins, Anton Pozniak
PURPOSE OF REVIEW: Antiretroviral (ARV) therapy costs in low-income and middle-income countries are major concerns, and lower doses of first-line treatment components, when possible, would save millions of dollars, which could be used to treat more people living with HIV. RECENT FINDINGS: The Encore-1 study, followed by a detailed pharmacokinetic analysis of efavirenz 400 versus 600 mg once daily, produced enough information for the most recent ARV treatment WHO guidelines to include efavirenz 400 mg among agents used for first-line treatment...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28561946/new-paradigm-for-translational-modeling-to-predict-long-term-tuberculosis-treatment-response
#19
I H Bartelink, N Zhang, R J Keizer, N Strydom, P J Converse, K E Dooley, E L Nuermberger, R M Savic
Disappointing results of recent tuberculosis chemotherapy trials suggest that knowledge gained from preclinical investigations was not utilized to maximal effect. A mouse-to-human translational pharmacokinetics (PKs) - pharmacodynamics (PDs) model built on a rich mouse database may improve clinical trial outcome predictions. The model included Mycobacterium tuberculosis growth function in mice, adaptive immune response effect on bacterial growth, relationships among moxifloxacin, rifapentine, and rifampin concentrations accelerating bacterial death, clinical PK data, species-specific protein binding, drug-drug interactions, and patient-specific pathology...
September 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28559276/population-pharmacokinetic-model-linking-plasma-and-peripheral-blood-mononuclear-cell-concentrations-of-efavirenz-and-its-metabolite-8-hydroxy-efavirenz-in-hiv-patients
#20
Abiy Habtewold, Eleni Aklillu, Eyasu Makonnen, Getnet Yimer, Leif Bertilsson, Jürgen Burhenne, Joel S Owen
The objectives of this study were to characterize the population pharmacokinetics (PK) of efavirenz (EFV) and 8-hydroxy-efavirenz (8OHEFV) in plasma and peripheral blood mononuclear cells (PBMCs) and to explore covariates affecting the PK parameters. Fifty-one patients had steady-state 0-to-24-h concentrations of EFV and 8OHEFV in plasma with corresponding concentrations in PBMCs, while 261 patients had one or two sparse concentrations at 16 ± 1 h postdose at weeks 4 and/or 16. The pharmacogenetic markers CYP2B6*6, CYP3A5*3, CYP3A5*6, UGT2B7*2, ABCB1 (3435C→T, 3842A→G), OATP1B1*1B, and OATP1B1*5, the presence of a rifampin-based antituberculosis (anti-TB) regimen, baseline body weight and organ function values, and demographic factors were explored as covariates...
August 2017: Antimicrobial Agents and Chemotherapy
keyword
keyword
117308
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"