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pharmacokinetics and TB

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https://www.readbyqxmd.com/read/28069654/reduced-chance-of-hearing-loss-associated-with-therapeutic-drug-monitoring-of-aminoglycosides-in-the-treatment-of-multidrug-resistant-tuberculosis
#1
R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar
Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto-)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of TB patients treated with amikacin or kanamycin in the period 2000 - 2012.Patients with culture-confirmed multi- or extensively drug resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28051340/altered-tolbutamide-pharmacokinetics-by-a-decrease-in-hepatic-expression-of-cyp2c6-11-in-rats-pretreated-with-5-fluorouracil
#2
Shuhei Fukuno, Katsuhito Nagai, Keita Kasahara, Yuki Mizobata, Sachiko Omotani, Yasutoshi Hatsuda, Michiaki Myotoku, Hiroki Konishi
We investigated the change in the pharmacokinetic profile of tolbutamide (TB), a substrate for CYP2C6/11, 4 days after single administration of 5-fluorouracil (5-FU), and the hepatic gene expression and activity of CYP2C6/11 were also examined in 5-FU-pretreated rats. Regarding the pharmacokinetic parameters of the 5-FU group, the area under the curve (AUC) was significantly increased, and correspondingly, the elimination rate constant at the terminal phase (ke) was significantly decreased without significant change in the volume of distribution at the steady state (Vdss)...
January 4, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28043864/a-simple-and-highly-effective-catalytic-nanozyme-scavenger-for-organophosphorus-neurotoxins
#3
Elena N Efremenko, Ilya V Lyagin, Natalia L Klyachko, Tatiana Bronich, Natalia V Zavyalova, Yuhang Jiang, Alexander V Kabanov
A simple and highly efficient catalytic scavenger of poisonous organophosphorus compounds, based on organophosphorus hydrolase (OPH, EC 3.1.8.1), is produced in aqueous solution by electrostatic coupling of the hexahistidine tagged OPH (His6-OPH) and poly(ethylene glycol)-b-poly(l-glutamic acid) diblock copolymer. The resulting polyion complex, termed nano-OPH, has a spherical morphology and a diameter from 25nm to 100nm. Incorporation of His6-OPH in nano-OPH preserves catalytic activity and increases stability of the enzyme allowing its storage in aqueous solution for over a year...
December 31, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28043603/individualized-treatment-of-multidrug-resistant-tuberculosis-using-therapeutic-drug-monitoring
#4
Mathieu S Bolhuis, Onno W Akkerman, Marieke G G Sturkenboom, Wiel C M de Lange, Tjip S van der Werf, Jan-Willem C Alffenaar
OBJECTIVE/BACKGROUND: Globally, approximately 50% of patients with multidrug-resistant tuberculosis (MDR-TB) experience treatment failure. MDR-TB treatment is hindered by adverse events, toxicity of the second-line anti-TB drugs, logistics and costs, especially in low-income countries, and problems with medication adherence. Pharmacokinetic variability is also attributed as one of the reasons contributing to treatment failure. In our reference Tuberculosis Center Beatrixoord (University Medical Center Groningen, Groningen, The Netherlands), we strive to individualize treatment of all MDR-TB patients based on drug-susceptibility testing using minimal inhibitory concentrations and pharmacokinetic parameters...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043500/design-and-development-of-novel-inhibitors-for-the-treatment-of-latent-tuberculosis
#5
Rudraraju Srilakshmi Reshma, Perumal Yogeeswari, Dharmarajan Sriram
OBJECTIVE/BACKGROUND: "The captain of all these men of death", is the apt sobriquet for the age-old disease tuberculosis (TB). Despite the availability of many drugs, cases of increasing resistance in the forms of multi-drug and extensively drug-resistant TB and persistence [characteristic of Mycobacterium tuberculosis (MTB)] make the eradication of TB a nightmare. Approval of bedaquiline by the Food and Drug Administration focused attention on quinoline scaffolds for development of new anti-TB agents...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28038962/confirming-model-predicted-pharmacokinetic-interactions-between-bedaquiline-and-lopinavir-ritonavir-or-nevirapine-in-patients-with-hiv-and-drug-resistant-tuberculosis
#6
Margreke J E Brill, Elin M Svensson, Mishal Pandie, Gary Maartens, Mats O Karlsson
Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug-drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14)...
December 14, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27994440/use-of-bedaquiline-and-delamanid-in-diabetes-patients-clinical-and-pharmacological-considerations
#7
REVIEW
Minhui Hu, Chunlan Zheng, Feng Gao
Antituberculosis (anti-TB) treatment may be affected by both diabetes and hypoglycemic agents in patients with these 2 comorbidities. However, data supporting this conclusion relate only to standard anti-TB therapies. Sirturo(®) (bedaquiline) and Deltyba(®) (delamanid), novel drugs for multidrug-resistant tuberculosis (MDR-TB), are recommended for diabetes patients when another effective treatment regimen cannot be provided. Currently, there are no clinical data related to the use of these agents in diabetes patients...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27955992/pediatric-multidrug-resistant-tuberculosis-clinical-trials-challenges-and-opportunities
#8
REVIEW
S E McAnaw, A C Hesseling, J A Seddon, K E Dooley, A J Garcia-Prats, S Kim, H E Jenkins, H S Schaaf, T R Sterling, C R Horsburgh
On June 17, 2016, RESIST-TB, IMPAACT, Vital Strategies, and New Ventures jointly hosted the Pediatric Multidrug Resistant Tuberculosis Clinical Trials Landscape Meeting in Arlington, Virginia, USA. The meeting provided updates on current multidrug-resistant tuberculosis (MDR-TB) trials targeting pediatric populations and adult trials that have included pediatric patients. A series of presentations were given that discussed site capacity needs, community engagement, and additional interventions necessary for clinical trials to improve the treatment of pediatric MDR-TB...
December 9, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27863179/population-pharmacokinetics-of-bedaquiline-and-metabolite-m2-in-patients-with-drug-resistant-tuberculosis-the-effect-of-time-varying-weight-and-albumin
#9
E M Svensson, A-G Dosne, M O Karlsson
Albumin concentration and body weight are altered in patients with multidrug-resistant tuberculosis (MDR-TB) and change during the long treatment period, potentially affecting drug disposition. We here describe the pharmacokinetics (PKs) of the novel anti-TB drug bedaquiline and its metabolite M2 in 335 patients with MDR-TB receiving 24 weeks of bedaquiline on top of a longer individualized background regimen. Semiphysiological models were developed to characterize the changes in weight and albumin over time...
December 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27855070/pharmacokinetics-of-the-first-line-antituberculosis-drugs-in-ghanaian-children-with-tuberculosis-with-and-without-hiv-coinfection
#10
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/27832142/predictors-of-prolonged-tb-treatment-in-a-dutch-outpatient-setting
#11
Natasha Van't Boveneind-Vrubleuskaya, Alper Daskapan, Jos G W Kosterink, Tjip S van der Werf, Susan van den Hof, Jan-Willem C Alffenaar
INTRODUCTION: Standard treatment duration for drug-susceptible tuberculosis (TB) treatment is 6 months. Treatment duration is often extended-and for various different reasons. The aim of this study was to determine the prevalence and to assess risk factors associated with extended TB treatment. METHODS: A cross-sectional study was conducted. Data including demographic, clinical, radiological and microbiological information from the Netherlands TB Register (NTR) of 90 patients with smear and culture positive pulmonary TB of the region Haaglanden, The Netherlands, was eligible for analysis...
2016: PloS One
https://www.readbyqxmd.com/read/27798208/mechanisms-of-action-and-therapeutic-efficacies-of-the-lipophilic-antimycobacterial-agents-clofazimine-and-bedaquiline
#12
REVIEW
Moloko C Cholo, Maborwa T Mothiba, Bernard Fourie, Ronald Anderson
Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis...
October 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27795624/rifampicin-and-anti-hypertensive-drugs-in-chronic-kidney-disease-pharmacokinetic-interactions-and-their-clinical-impact
#13
A Agrawal, S K Agarwal, T Kaleekal, Y K Gupta
Patients on dialysis have an increased incidence of tuberculosis (TB). Rifampicin, a first-line antitubercular therapy (ATT) drug, is a potent inducer of hepatic cytochrome P450 (CYP). There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation...
September 2016: Indian Journal of Nephrology
https://www.readbyqxmd.com/read/27792837/isoniazid-clearance-is-impaired-among-human-immunodeficiency-virus-tuberculosis-patients-with-high-levels-of-immune-activation
#14
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...
October 28, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27776583/carbapenems-against-mycobacterium-tuberculosis-a-review-of-the-evidence
#15
D Jaganath, G Lamichhane, M Shah
Carbapenems, a more recent β-lactam class, represent a unique anti-tuberculosis option, as emerging evidence demonstrates that they target the Mycobacterium tuberculosis cell wall and β-lactamase. This provides a potentially new agent against M. tuberculosis, in particular for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), where options are limited. In this review, we examine the current evidence on the activity of carbapenems against M. tuberculosis. The predominance of work is in vitro, and suggests that carbapenems kill M...
November 2016: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/27775177/recent-advances-and-structural-features-of-enoyl-acp-reductase-inhibitors-of-mycobacterium-tuberculosis
#16
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/27724114/the-challenges-of-pharmacokinetic-variability-of-first-line-anti-tb-drugs
#17
Bella Devaleenal Daniel, 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'...
January 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27704782/essential-but-not-vulnerable-indazole-sulfonamides-targeting-inosine-monophosphate-dehydrogenase-as-potential-leads-against-mycobacterium-tuberculosis
#18
Yumi Park, Angela Pacitto, Tracy Bayliss, Laura A T Cleghorn, Zhe Wang, Travis Hartman, Kriti Arora, Thomas R Ioerger, Jim Sacchettini, Menico Rizzi, Stefano Donini, Tom L Blundell, David B Ascher, Kyu Y Rhee, Ardala Breda, Nian Zhou, Veronique Dartois, Surendranadha Reddy Jonnala, Laura E Via, Valerie Mizrahi, Ola Epemolu, Laste Stojanovski, Frederick Ryan Carne Simeons, Maria Osuna-Cabello, Lucy Ellis, Claire J MacKenzie, Alasdair R C Smith, Susan Helen Davis, Dinakaran Murugesan, Kirsteen I Buchanan, Penelope A Turner, Margaret Huggett, Fabio Zuccotto, Maria Jose Rebollo-Lopez, Maria Jose Lafuente-Monasterio, Olalla Sanz, Gracia Santos Diaz, Joël Lelièvre, Lluis Ballell, Carolyn Selenski, Matthew Axtman, Sonja Ghidelli-Disse, Hannah Pflaumer, Markus Boesche, Gerard Drewes, Gail Freiberg, Matthew D Kurnick, Myron Srikumaran, Dale J Kempf, Simon R Green, Peter Christopher Ray, Kevin D Read, Paul G Wyatt, Clifton E Barry Rd, Helena I M Boshoff
A potent, non-cytotoxic indazole sulfonamide was identified by high-throughput screening of >100,000 synthetic compounds for activity against Mycobacterium tuberculosis (Mtb). This non-cytotoxic compound did not directly inhibit cell wall biogenesis but triggered a slow lysis of Mtb cells as measured by release of intracellular green fluorescent protein (GFP). Isolation of resistant mutants followed by whole-genome sequencing showed an unusual gene amplification of a 40 gene region spanning Rv3371 to Rv3411c and in one case a potential promoter mutation upstream of guaB2 (Rv3411c) encoding inosine monophosphate dehydrogenase (IMPDH)...
October 5, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27693714/the-implications-of-model-informed-drug-discovery-and-development-for-tuberculosis
#19
Morris Muliaditan, Geraint R Davies, Ulrika S H Simonsson, Stephen H Gillespie, Oscar Della Pasqua
Despite promising advances in the field and highly effective first-line treatment, an estimated 9.6 million people are still infected with tuberculosis (TB). Innovative methods are required to effectively transition the growing number of compounds into novel combination regimens. However, progression of compounds into patients occurs despite the lack of clear understanding of the pharmacokinetic-pharmacodynamic (PK/PD) relations. The PreDiCT-TB consortium was established in response to the existing gaps in TB drug development...
September 28, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27576453/effect-of-peg-and-water-soluble-chitosan-coating-on-moxifloxacin-loaded-plga-long-circulating-nanoparticles
#20
Sanaul Mustafa, V Kusum Devi, Roopa S Pai
Moxifloxacin (MOX) is a Mycobacterium tuberculosis DNA gyrase inhibitor. Due to its intense hydrophilicity, MOX is cleared from the body within 24 h and required for repetitive doses which may then result in hepatotoxicity and acquisition of MOX resistant-TB, related with its use. To overcome the aforementioned limitations, the current study aimed to develop PLGA nanoparticles (PLGA NPs), to act as an efficient carrier for controlled delivery of MOX. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to MOX-PLGA NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was rose for surface modification of NPs...
August 30, 2016: Drug Delivery and Translational Research
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