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pharmacokinetics and TB

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https://www.readbyqxmd.com/read/28193650/interaction-of-rifampicin-and-darunavir-ritonavir-or-darunavir-cobicistat-in-vitro
#1
Owain Roberts, Saye Khoo, Andrew Owen, Marco Siccardi
Treatment of HIV patients co-infected with tuberculosis (TB) is challenging due to drug-drug interactions (DDIs) between antiretrovirals (ARVs) and anti-TB drugs. The aim of this study was to quantify the effects of cobicistat (COBI), or ritonavir (RTV), in modulating DDIs between darunavir (DRV) and rifampicin (RIF) in a human hepatocyte-based in vitro model. Human primary hepatocyte cultures were incubated with RIF alone, or in combination with either COBI or RTV for three days, followed by co-incubation with DRV for one hour...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28163165/the-risk-of-global-epidemic-replacement-with-drug-resistant-mycobacterium-tuberculosis-strains
#2
REVIEW
Emma S McBryde, Michael T Meehan, Tan N Doan, Romain Ragonnet, Ben J Marais, Vanina Guernier, James M Trauer
OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) is a threat to tuberculosis (TB) control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. The issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. This evidence was then synthesized into a mathematical model. METHODS: This model considers two TB strains, one with and one without an MDR phenotype...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28162875/diagnosis-of-spinal-lesions-using-heuristic-and-pharmacokinetic-parameters-measured-by-dynamic-contrast-enhanced-mri
#3
Ning Lang, Huishu Yuan, Hon J Yu, Min-Ying Su
RATIONALE AND OBJECTIVES: This study aimed to evaluate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiation of four spinal lesions by using heuristic and pharmacokinetic parameters analyzed from DCE signal intensity time course. MATERIALS AND METHODS: DCE-MRI of 62 subjects with confirmed myeloma (n = 9), metastatic cancer (n = 22), lymphoma (n = 7), and inflammatory tuberculosis (TB) (n = 24) in the spine were analyzed retrospectively...
February 2, 2017: Academic Radiology
https://www.readbyqxmd.com/read/28160272/suboptimal-exposure-to-anti-tb-drugs-in-a-tbm-hiv-population-is-not-related-to-anti-retroviral-therapy
#4
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/28141813/determination-of-plasma-concentrations-of-levofloxacin-by-high-performance-liquid-chromatography-for-use-at-a-multidrug-resistant-tuberculosis-hospital-in-tanzania
#5
Andrew Ebers, Suzanne Stroup, Stellah Mpagama, Riziki Kisonga, Isaack Lekule, Jie Liu, Scott Heysell
Therapeutic drug monitoring may improve multidrug-resistant tuberculosis (MDR-TB) treatment outcomes. Levofloxacin demonstrates significant individual pharmacokinetic variability. Thus, we sought to develop and validate a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection for levofloxacin in patients on MDR-TB treatment. The HPLC-UV method is based on a solid phase extraction (SPE) and a direct injection into the HPLC system. The limit of quantification was 0.25 μg/mL, and the assay was linear over the concentration range of 0...
2017: PloS One
https://www.readbyqxmd.com/read/28137814/pharmacokinetic-modeling-and-limited-sampling-strategies-based-on-healthy-volunteers-for-monitoring-of-ertapenem-in-mdr-tb-patients
#6
S P van Rijn, M A Zuur, R van Altena, O W Akkerman, J H Proost, W C M de Lange, H A M Kerstjens, D J Touw, T S van der Werf, J G W Kosterink, J W C Alffenaar
BACKGROUND: Ertapenem is a broad spectrum carbapenem antibiotic and is being explored against Mycobacterium tuberculosis Carbapenems have anti-bacterial activity when the plasma concentration exceeds the minimal inhibitory concentration at least 40% of the time (40%T>MIC). To assess 40%T>MIC in multidrug-resistant tuberculosis (MDR-TB) patients, a limited sampling strategy was developed using a population pharmacokinetic model based on healthy volunteers. METHODS: A two-compartment population pharmacokinetic model was developed from data in forty-two healthy volunteers, using an iterative two-stage Bayesian method...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28111912/in-silico-approaches-and-chemical-space-of-anti-p-type-atpase-compounds-for-discovering-new-antituberculous-drugs
#7
REVIEW
Paola Santos, Fabian López-Vallejo, Carlos-Y Soto
Tuberculosis (TB) is one of the most important public health problems around the world. The emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains has driven the finding of alternative anti-TB targets. In this context, P-type ATPases are interesting therapeutic targets due to their key role in ion homeostasis across the plasma membrane and the mycobacterial survival inside macrophages. In this review, in silico and experimental strategies used for the rational design of new anti-TB drugs are presented; in addition, the chemical space distribution based on the structure and molecular properties of compounds with anti-TB and anti-P-type ATPase activity is discussed...
January 22, 2017: Chemical Biology & Drug Design
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
#8
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
#9
Shuhei Fukuno, Katsuhito Nagai, Keita Kasahara, Yuki Mizobata, Sachiko Omotani, Yasutoshi Hatsuda, Michiaki Myotoku, Hiroki Konishi
1. 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. 2. 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 31, 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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-or-without-hiv-coinfection
#17
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/27832142/predictors-of-prolonged-tb-treatment-in-a-dutch-outpatient-setting
#18
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
#19
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
#20
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
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