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isoniazid pharmacokinetics

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https://www.readbyqxmd.com/read/29133558/pharmacokinetics-and-drug-drug-interactions-of-lopinavir-ritonavir-administered-with-first-and-second-line-antituberculosis-drugs-in-hiv-infected-children-treated-for-multidrug-resistant-tuberculosis
#1
Louvina E van der Laan, Anthony J Garcia-Prats, H Simon Schaaf, Tjokosela Tikiso, Lubbe Wiesner, Mine de Kock, Jana Winckler, Jennifer Norman, Helen McIlleron, Paolo Denti, Anneke C Hesseling
Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29120971/a-systematic-review-of-salivary-versus-blood-concentrations-of-anti-tuberculosis-drugs-and-their-potential-for-salivary-therapeutic-drug-monitoring
#2
Simone H J van den Elsen, Lisette M Oostenbrink, Scott K Heysell, Daiki Hira, Daan J Touw, Onno W Akkerman, Mathieu S Bolhuis, Jan-Willem C Alffenaar
BACKGROUND: Therapeutic drug monitoring is useful in the treatment of tuberculosis to assure adequate exposure, minimize antibiotic resistance, and reduce toxicity. Salivary therapeutic drug monitoring could reduce the risks, burden, and costs of blood-based therapeutic drug monitoring. This systematic review compared human pharmacokinetics of anti-tuberculosis drugs in saliva and blood to determine if salivary therapeutic drug monitoring could be a promising alternative. METHODS: On December 2, 2016, PubMed and the Institute for Scientific Information Web of Knowledge were searched for pharmacokinetic studies reporting human salivary and blood concentrations of anti-tuberculosis drugs...
November 8, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29050764/pharmacokinetic-studies-of-a-three-component-complex-that-repurposes-the-front-line-antibiotic-isoniazid-against-mycobacterium-tuberculosis
#3
Thomas J Manning, Kyle Wilkerson, Taylor Holder, Andrew Carson Bartley, Chelsea Jackson, Sydney Plummer, Dennis Phillips, Logan Krajewski, Greg Wylie
The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a three component complex aimed at increasing the delivery efficiency and adding new avenues to its mechanism of action. This study focuses on pharmacokinetic studies of the isoniazid-sucrose-copper (II)-PEG-3350 complex. The assays include the Plasma Protein Binding Assay (85.8%), Caco-2 Permeability Assay (B→APapp, 0.13 × 10(-6) cm/s), Cytochrome P450 Inhibition Assay (i.e. CYP2B6, IC50 = 7.26 μM), In vitro microsomal Stability Assay (t1/2 NADPH-Dependent > 240 min), and HepG2 Cytotoxicity (no toxicity)...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29037995/preclinical-pharmacokinetic-profiling-of-iqg-607-a-potential-oral-metallodrug-to-treat-tuberculosis
#4
Adilio da S Dadda, Valnês S Rodrigues-Junior, Fernando Carreño, Guilherme O Petersen, Antônio F M Pinto, Pedro F Dalberto, Nathalia D M Sperotto, Kenia Pissinate, Cristiano V Bizarro, Pablo Machado, Maria M Campos, Teresa Dalla Costa, Diógenes S Santos, Luiz A Basso
IQG-607 is an analog of isoniazid with anti-tuberculosis activity. This work describes the development and validation of an HPLC method to quantify pentacyano(isoniazid)ferrate(II) compound (IQG-607) and the pharmacokinetic studies of this compound in mice. The method showed linearity in the 0.5-50μg/mL concentration range (r=0.9992). Intra- and inter-day precision was <5%, and the recovery ranged from 92.07 to 107.68%. IQG-607 was stable in plasma for at least 30days at -80°C and, after plasma processing, for 4h in the auto-sampler maintained on ice (recovery >85%)...
October 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29017426/investigations-on-the-influence-of-zidovudine-in-the-pharmacokinetics-of-isoniazid-and-its-hepatotoxic-metabolites-in-rats
#5
Raghu Ramanathan, Karthikeyan Sivanesan
The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28993169/anti-tuberculosis-drug-combination-for-controlled-oral-delivery-using-3d-printed-compartmental-dosage-forms-from-drug-product-design-to-in-vivo-testing
#6
Natalja Genina, Johan Peter Boetker, Stefano Colombo, Necati Harmankaya, Jukka Rantanen, Adam Bohr
The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion (HME) of the drug-containing filaments...
October 6, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28862186/food-significantly-reduces-plasma-concentrations-of-first-line-anti-tuberculosis-drugs
#7
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/28835350/development-of-water-soluble-3-5-dinitrophenyl-tetrazole-and-oxadiazole-antitubercular-agents
#8
Jaroslav Roh, Galina Karabanovich, Hana Vlčková, Alejandro Carazo, Jan Němeček, Pavel Sychra, Lenka Valášková, Oto Pavliš, Jiřina Stolaříková, Věra Klimešová, Kateřina Vávrová, Petr Pávek, Alexandr Hrabálek
In this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N-benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against Mycobacterium tuberculosis CNCTC My 331/88 (H37Rv), comparable to those of the first-line drugs isoniazid and rifampicin...
October 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28827417/pharmacokinetics-tolerability-and-bacteriological-response-of-rifampin-administered-at-600-900-and-1-200-milligrams-daily-in-patients-with-pulmonary-tuberculosis
#9
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
In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months...
November 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28741299/a-review-of-moxifloxacin-for-the-treatment-of-drug-susceptible-tuberculosis
#10
REVIEW
Anushka Naidoo, Kogieleum Naidoo, Helen McIlleron, Sabiha Essack, Nesri Padayatchi
Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance...
November 2017: Journal of Clinical Pharmacology
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/28657202/assessing-pharmacodynamic-interactions-in-mice-using-the-multistate-tuberculosis-pharmacometric-and-general-pharmacodynamic-interaction-models
#12
Chunli Chen, Sebastian G Wicha, Gerjo J de Knegt, Fatima Ortega, Laura Alameda, Veronica Sousa, Jurriaan E M de Steenwinkel, Ulrika S H Simonsson
The aim of this study was to investigate pharmacodynamic interactions in mice infected with Mycobacterium tuberculosis using population pharmacokinetics, the Multistate Tuberculosis Pharmacometric (MTP) model, and the General Pharmacodynamic Interaction (GPDI) model. Rifampicin, isoniazid, ethambutol or pyrazinamide were administered in monotherapy for 4 weeks. Rifampicin and isoniazid showed effects in monotherapy, whereas the animals became moribund after 7 days with ethambutol or pyrazinamide alone. No pharmacodynamic interactions were observed against fast-multiplying bacteria...
June 28, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28653479/a-population-pharmacokinetic-model-incorporating-saturable-pharmacokinetics-and-autoinduction-for-high-rifampicin-doses
#13
Robin J Svensson, Rob E Aarnoutse, Andreas H Diacon, Rodney Dawson, Stephen H Gillespie, Martin J Boeree, Ulrika S H Simonsson
Accumulating evidence suggests that increasing doses of rifampicin may shorten tuberculosis treatment. The PanACEA HIGHRIF1 trial assessed safety, pharmacokinetics, and antimycobacterial activity of rifampicin at doses up to 40 mg/kg. Eighty-three pulmonary tuberculosis patients received 10, 20, 25, 30, 35, or 40 mg/kg rifampicin daily over 2 weeks, supplemented with standard doses of isoniazid, pyrazinamide, and ethambutol in the second week. This study aimed at characterizing rifampicin pharmacokinetics observed in HIGHRIF1 using nonlinear mixed effects modeling...
June 27, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28607022/pharmacokinetics-of-pyrazinamide-and-optimal-dosing-regimens-for-drug-sensitive-and-resistant-tuberculosis
#14
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/28506804/chloroquine-enhances-the-antimycobacterial-activity-of-isoniazid-and-pyrazinamide-by-reversing-inflammation-induced-macrophage-efflux
#15
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...
July 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
#16
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...
July 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28419277/prevention-of-tb-using-rifampicin-plus-isoniazid-reduces-nevirapine-concentrations-in-hiv-exposed-infants
#17
Helen McIlleron, Paolo Denti, Silvia Cohn, Fildah Mashabela, Jennifer D Hoffmann, Saba Shembe, Regina Msandiwa, Lubbe Wiesner, Sithembiso Velaphi, Sanjay G Lala, Richard E Chaisson, Neil Martinson, Kelly E Dooley
Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis...
July 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333192/susceptibilities-of-mdr-mycobacterium-tuberculosis-isolates-to-unconventional-drugs-compared-with-their-reported-pharmacokinetic-pharmacodynamic-parameters
#18
Joseph S Cavanaugh, Ruwen Jou, Mei-Hua Wu, Tracy Dalton, Ekaterina Kurbatova, Julia Ershova, J Peter Cegielski
Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28160272/suboptimal-exposure-to-anti-tb-drugs-in-a-tbm-hiv-population-is-not-related-to-anti-retroviral-therapy
#19
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/28157477/pharmacokinetics-and-pharmacodynamics-of-isoniazid-in-patients-with-intermediate-resistance
#20
Abdullah Alsultan, Charles A Peloquin
No abstract text is available yet for this article.
January 1, 2017: International Journal of Tuberculosis and Lung Disease
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