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Tuberculosis pharmacokinetics

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https://www.readbyqxmd.com/read/28546104/development-of-a-paediatric-physiologically-based-pharmacokinetic-model-to-assess-the-impact-of-drug-drug-interactions-in-tuberculosis-co-infected-malaria-subjects-a-case-study-with-artemether-lumefantrine-and-the-cyp3a4-inducer-rifampicin
#1
Olusola Olafuyi, Michael Coleman, Raj K S Badhan
The fixed dosed combination of artemether and lumefantrine (AL) is widely used for the treatment of malaria in adults and children in sub-Sahara Africa, with lumefantrine day 7 concentrations being widely used as a marker for clinical efficacy. Both are substrates for CYP3A4 and susceptible to drug-drug interactions (DDIs); indeed, knowledge of the impact of these factors is currently sparse in paediatric population groups. Confounding malaria treatment is the co-infection of patients with tuberculosis. The concomitant treatment of AL with tuberculosis chemotherapy, which includes the CYP3A4 inducer rifampicin, increases the risk of parasite recrudescence and malaria treatment failure...
May 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28528008/-role-of-therapeutic-drug-monitoring-in-pulmonary-infections
#2
REVIEW
C Padoin
Pulmonary infections are common and caused by a wide range of viruses, bacteria, parasites and fungi. They consist of lower respiratory tract infections with community and hospital acquired acute pneumonia, bronchitis, lung abscess, fungal infections and tuberculosis. The management of these infections should be based on guidelines that take into account the microorganisms most frequently involved as a basis for empirical treatment, with identification of causative microorganisms allowing targeted treatments...
May 17, 2017: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/28523106/discovery-of-fluorine-containing-benzoxazinyl-oxazolidinones-for-the-treatment-of-multidrug-resistant-tuberculosis
#3
Hongyi Zhao, Yu Lu, Li Sheng, Zishuo Yuan, Bin Wang, Weiping Wang, Yan Li, Chen Ma, Xiaoliang Wang, Dongfeng Zhang, Haihong Huang
A novel series of fluorine-containing benzoxazinyl-oxazolidinones were designed and synthesized as antidrug-resistant tuberculosis agents possessing good activity and improved pharmacokinetic profiles. Compound 21 exhibited not only outstanding in vitro activity with a MIC value of 0.25-0.50 μg/mL against drug-susceptible H37Rv strain and two clinically isolated drug-resistant Mycobacterium tuberculosis strains, but also acceptable in vitro ADME/T properties. Moreover, this compound displayed excellent mouse pharmacokinetic profiles with an oral bioavailability of 102% and a longer elimination half-life of 4...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28518128/an-in-vitro-caseum-binding-assay-that-predicts-drug-penetration-in-tuberculosis-lesions
#4
Jansy P Sarathy, Hsin-Pin Ho Liang, Danielle Weiner, Jacqueline Gonzales, Laura E Via, Véronique Dartois
The eradication of tuberculosis disease requires drug regimens that can penetrate the multiple layers of complex pulmonary lesions. Drug distribution in the caseous cores of cavities and lesions is especially crucial because they harbor subpopulations of drug-tolerant bacteria also commonly referred to as persisters. Existing methods for the measurement of drug penetration in tuberculosis lesions involve costly and time-consuming in vivo pharmacokinetic studies coupled to bioanalytical or imaging techniques...
May 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28510480/dry-powder-inhaler-formulation-of-rifampicin-an-improved-targeted-delivery-system-for-alveolar-tuberculosis
#5
Tejal Rawal, Laurent Kremer, Iman Halloum, Shital Butani
BACKGROUND: The delivery of antitubercular drugs through direct lung targeting can lead to reduction in the dose as well as side effects of the drug. In the present investigation, carrier (lactose)-based dry-powder inhaler of rifampicin was prepared to achieve direct targeting of the drug into the lungs. METHODS: The dry powder inhaler formulation was prepared by simply mixing micronized rifampicin with coarse and fine lactose preblend. Preliminary blends of the drug were prepared with various lactose grades (Inhalac(®), Respitose,(®) and Lactohale(®))...
May 16, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28510418/conjugation-reaction-with-8-arm-peg-markedly-improves-the-immunogenicity-of-mycobacterium-tuberculosis-cfp10-tb10-4-fusion-protein
#6
Xiaowei Sun, Weili Yu, Quanhai Pang, Tao Hu
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for tuberculosis (TB). Effective vaccination is highly desired for immunoprotection against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb-secreted protein antigens, which suffer from poor immunogenicity. Thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. CFP10 and TB10.4 are two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen...
May 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28507117/pharmacokinetics-of-levofloxacin-in-multidrug-and-extensively-drug-resistant-tuberculosis-patients
#7
Natasha Van't Boveneind-Vrubleuskaya, Tatiana Seuruk, Kai van Hateren, Tridia van der Laan, Jos G W Kosterink, Tjip S van der Werf, Dick van Soolingen, Susan van den Hof, Alena Skrahina, Jan-Willem C Alffenaar
Pharmacodynamics are important in treatment of especially multidrug- and extensively resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to minimal inhibitory concentration (fAUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter to predict the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for fAUC/MIC ratios. Patients with pulmonary M/XDR-TB received LFX as part of treatment regimen at a dose of 15 mg/kg once daily...
May 15, 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
#8
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
#9
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...
May 8, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28461315/genetic-determinants-of-the-pharmacokinetic-variability-of-rifampicin-in-malawian-adults-with-pulmonary-tuberculosis
#10
Derek J Sloan, Andrew D McCallum, Alessandro Schipani, Deirdre Egan, Henry C Mwandumba, Steve A Ward, David Waterhouse, Gertrude Banda, Theresa J Allain, Andrew Owen, Saye H Khoo, Geraint R Davies
Variable exposure to anti-tuberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampicin. We evaluated the contribution of Single Nucleotide Polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC, CES-1) to inter-individual pharmacokinetic variability in Malawi. 174 adults with pulmonary TB underwent sampling of plasma rifampicin concentrations at 2- and 6-hours post-dose...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28423019/design-synthesis-and-structure-activity-relationship-study-of-wollamide-b-a-new-potential-anti-tb-agent
#11
Henok Asfaw, Katja Laqua, Anna Maria Walkowska, Fraser Cunningham, Maria Santos Martinez-Martinez, Juan Carlos Cuevas-Zurita, Lluís Ballell-Pages, Peter Imming
Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural activity relationship (SAR), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial activities of wollamide B and all the synthesized analogues were tested against Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and pharmacokinetic (ADME) profiling was done for the synthesized compounds to evaluate their drug likeness...
2017: PloS One
https://www.readbyqxmd.com/read/28408267/population-pharmacokinetics-of-moxifloxacin-cycloserine-p-aminosalicylic-acid-and-kanamycin-for-the-treatment-of-multi-drug-resistant-tuberculosis
#12
Min Jung Chang, Byunghak Jin, Jung-Woo Chae, Hwi-Yeol Yun, Eun Sun Kim, Yeon Joo Lee, Young-Jae Cho, Ho Il Yoon, Choon-Taek Lee, Kyoung Un Park, Junghan Song, Jae-Ho Lee, Jong Sun Park
Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28389352/simple-strategy-to-assess-linezolid-exposure-in-patients-with-multi-drug-resistant-and-extensively-drug-resistant-tuberculosis
#13
Jasper Kamp, Mathieu S Bolhuis, Simon Tiberi, Onno W Akkerman, Rosella Centis, Wiel C de Lange, Jos G Kosterink, Tjip S van der Werf, Giovanni B Migliori, Jan-Willem C Alffenaar
Linezolid is used increasingly for the treatment of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis (TB). However, linezolid can cause severe adverse events, such as peripheral and optical neuropathy or thrombocytopenia related to higher drug exposure. This study aimed to develop a population pharmacokinetic model to predict the area under the concentration curve (AUC) for linezolid using a limited number of blood samples. Data from patients with MDR-/XDR-TB who received linezolid and therapeutic drug monitoring as part of their TB treatment were used...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28387740/protective-effect-of-bicyclol-on-anti-tuberculosis-drug-induced-liver-injury-in-rats
#14
Xin Liu, Manman Zhao, Jiaqi Mi, Hui Chen, Li Sheng, Yan Li
The present study was performed to investigate the effect of bicyclol, a synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory properties, on anti-tuberculosis (anti-TB) drug-induced liver injury and related mechanisms in rats. Bicyclol was given to rats by gavage 2 h before the oral administration of an anti-TB drug once a day for 30 days. Liver injury was evaluated by biochemical and histopathological examinations. Lipid peroxidation, mitochondrial function, and the activity of antioxidants were measured by spectrophotometric methods...
April 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28363192/rifampicin-loaded-chitosan-nanoparticle-dry-powder-presents-an-improved-therapeutic-approach-for-alveolar-tuberculosis
#15
Tejal Rawal, Rajesh Parmar, Rajeev K Tyagi, Shital Butani
Current treatment therapeutic approach for tuberculosis is the administration of first line drugs in the form of tablets and capsules for 4-6 months. However, this approach leads to severe adverse effects. Therefore, present study was designed to achieving local and sustained targeting of anti-tubercular drugs in order to reduce dose and frequency. The nanoparticle based dry powder formulation of rifampicin was developed and analyzed with respect to its direct targeting potential of lungs. Rifampicin loaded nanoparticles were formulated by ionic gelation probe sonication method, and characterized with respect to particle size, zeta potential, entrapment and drug loading efficiency...
June 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28356552/pharmacokinetic-pharmacodynamic-modelling-of-intracellular-mycobacterium-tuberculosis-growth-and-kill-rates-is-predictive-of-clinical-treatment-duration
#16
Ghaith Aljayyoussi, Victoria A Jenkins, Raman Sharma, Alison Ardrey, Samantha Donnellan, Stephen A Ward, Giancarlo A Biagini
Tuberculosis (TB) treatment is long and complex, typically involving a combination of drugs taken for 6 months. Improved drug regimens to shorten and simplify treatment are urgently required, however a major challenge to TB drug development is the lack of predictive pre-clinical tools. To address this deficiency, we have adopted a new high-content imaging-based approach capable of defining the killing kinetics of first line anti-TB drugs against intracellular Mycobacterium tuberculosis (Mtb) residing inside macrophages...
March 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28353169/the-effect-of-single-and-multiple-doses-of-rifampin-on-the-pharmacokinetics-of-doravirine-in-healthy-subjects
#17
Ka Lai Yee, Sauzanne G Khalilieh, Rosa I Sanchez, Rachael Liu, Matt S Anderson, Helen Manthos, Timothy Judge, John Brejda, Joan R Butterton
BACKGROUND AND OBJECTIVE: Doravirine is a novel, next-generation, non-nucleoside reverse transcriptase inhibitor in development for the treatment of human immunodeficiency virus-1 infection in combination with other antiretrovirals. Doravirine is a substrate for cytochrome P450 (CYP) 3A and P-glycoprotein. Rifampin (rifampicin) is used for treating tuberculosis in patients who are co-infected with human immunodeficiency virus. Rifampin demonstrates organic anion-transporting polypeptide 1B1 and P-glycoprotein inhibition after single-dose administration and CYP3A and P-glycoprotein induction after multiple-dose administration...
March 28, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28352475/kanamycin-sulphate-loaded-plga-vitamin-e-tpgs-long-circulating-nanoparticles-using-combined-coating-of-peg-and-water-soluble-chitosan
#18
Sanaul Mustafa, V Kusum Devi, Roopa S Pai
Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. Due to its intense hydrophilicity, KS is cleared from the body within 8 h. KS has a very short plasma half-life (2.5 h). KS is used in high concentrations to reach the therapeutic levels in plasma, which results in serious nephrotoxicity/ototoxicity. To overcome aforementioned limitations, the current study aimed to develop KS loaded PLGA-Vitamin-E-TPGS nanoparticles (KS-PLGA-TPGS NPs), to act as an efficient carrier for controlled delivery of KS...
2017: Journal of Drug Delivery
https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#19
REVIEW
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis)...
March 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28333284/revisiting-the-mutant-prevention-concentration-to-guide-dosing-in-childhood-tuberculosis
#20
Devan Jaganath, H Simon Schaaf, Peter R Donald
The mutant prevention concentration (MPC) is a well-known concept in the chemotherapy of many bacterial infections, but is seldom considered in relation to tuberculosis (TB) treatment, as the required concentrations are generally viewed as unachievable without undue toxicity. Early studies revealed single mutations conferring high MICs of first- and second-line anti-TB agents; however, the growing application of genomics and quantitative drug susceptibility testing in TB suggests a wide range of MICs often determined by specific mutations and strain type...
March 9, 2017: Journal of Antimicrobial Chemotherapy
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