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isoniazid pharmacokinetics

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https://read.qxmd.com/read/30767706/effects-of-genetic-variability-on-rifampicin-and-isoniazid-pharmacokinetics-in-south-african-patients-with-recurrent-tuberculosis
#1
Anushka Naidoo, Maxwell Chirehwa, Veron Ramsuran, Helen McIlleron, Kogieleum Naidoo, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ncgapu, John Adamson, Katya Govender, Paolo Denti, Nesri Padayatchi
AIM: We report the prevalence and effect of genetic variability on pharmacokinetic parameters of isoniazid and rifampicin. MATERIALS & METHODS: Genotypes for SLCO1B1, NAT2, PXR, ABCB1 and UGT1A genes were determined using a TaqMan® Genotyping OpenArray™. Nonlinear mixed-effects models were used to describe drug pharmacokinetics. RESULTS: Among 172 patients, 18, 43 and 34% were classified as rapid, intermediate and slow NAT2 acetylators, respectively...
February 15, 2019: Pharmacogenomics
https://read.qxmd.com/read/30723406/exposure-of-infants-to-isoniazid-via-breast-milk-after-maternal-drug-intake-of-recommended-doses-is-clinically-insignificant-irrespective-of-metaboliser-status-a-physiologically-based-pharmacokinetic-pbpk-modelling-approach-to-estimate-drug-exposure-of-infants
#2
Estella Dora Germaine Garessus, Hans Mielke, Ursula Gundert-Remy
Isoniazid is a first-line anti-tuberculosis drug recommended for treatment of drug-susceptible Mycobacterium tuberculosis infections. Breast-feeding is not contra-indicated while undergoing isoniazid therapy, even though isoniazid was found to migrate into breast milk, leading to infant drug exposure. Exposure assessment of isoniazid in infants exposed to the drug via breast milk has so far not accounted for the polymorphic expression of the isoniazid metabolising enzyme N -acetyltransferase 2. The aim of this study was to re-visit the safety assessment of maternal isoniazid therapy for infants exposed to the drug via breast milk, while accounting for fast and slow metabolisers in the adult and infant population, as well as for slower metabolism in small infants than in adults...
2019: Frontiers in Pharmacology
https://read.qxmd.com/read/30694726/solid-lipid-nanoparticles-for-ocular-delivery-of-isoniazid-evaluation-proof-of-concept-and-in-vivo-safety-kinetics
#3
Mandeep Singh, Ana Guzman-Aranguez, Afzal Hussain, Cheerneni S Srinivas, Indu P Kaur
AIM: Evaluation of solid lipid nanoparticles (SLNs) for ocular delivery of isoniazid (INH). MATERIALS & METHODS: INH-SLNs were characterized for morphological, thermal, crystalline and nuclear magnetic resonance properties. In vitro release and ex vivo corneal permeability of INH-SLNs was also evaluated. Proof-of-concept uptake studies were performed in corneal and conjunctival cell lines and in vivo in rat eye using fluorescein-labeled SLNs. Antimycobacterial activity of INH-SLNs was confirmed...
January 29, 2019: Nanomedicine
https://read.qxmd.com/read/30588647/optimisation-of-dosing-regimens-of-isoniazid-and-rifampicin-in-children-with-tuberculosis-in-india
#4
Blessed Winston Aruldhas, Richard M Hoglund, Jaya Ranjalkar, Joel Tarning, Sumith K Mathew, Valsan Philip Verghese, Anuradha Bose, Binu Susan Mathew
BACKGROUND: Pharmacokinetic studies in the past have shown inadequate antituberculosis drug levels in children with the currently available dosing regimens. This study attempted to investigate the pharmacokinetics of isoniazid and rifampicin, when used in children, and to optimise their dosing regimens. METHODS: Data were collected from 41 children, aged 2 to 16 years, who were being treated with anti-tuberculosis drugs for at least 2 months. Concentration measurements were done for a 6-hour period and analysed using a non-linear, mixed-effects model...
December 26, 2018: British Journal of Clinical Pharmacology
https://read.qxmd.com/read/30572983/pharmacokinetics-of-isoniazid-in-indian-children-with-tuberculosis-on-daily-treatment
#5
I Shah, N Jadhao, N Mali, S Deshpande, N Gogtay, U Thatte
<h2>OBJECTIVE:</h2>To assess the pharmacokinetics of isoniazid (INH) at 10 mg/kg/day among Indian children.<h2>METHODS:</h2>INH levels were estimated using liquid chromatography-tandem mass spectroscopy in 35 children aged 1&ndash;15 years on daily anti-tuberculosis treatment. Blood samples were collected 0, 1, 2, 3, 6 and 24 h after INH administration. The maximum concentration (Cmax ) and area under the curve (AUC0&ndash;24 ) were determined. The normal therapeutic range for Cmax is 3&ndash;5 &mu;g/ml...
December 20, 2018: International Journal of Tuberculosis and Lung Disease
https://read.qxmd.com/read/30563908/synergistic-lethality-of-a-binary-inhibitor-of-mycobacterium-tuberculosis-kasa
#6
Pradeep Kumar, Glenn C Capodagli, Divya Awasthi, Riju Shrestha, Karishma Maharaja, Paridhi Sukheja, Shao-Gang Li, Daigo Inoyama, Matthew Zimmerman, Hsin Pin Ho Liang, Jansy Sarathy, Marizel Mina, George Rasic, Riccardo Russo, Alexander L Perryman, Todd Richmann, Aditi Gupta, Eric Singleton, Sheetal Verma, Seema Husain, Patricia Soteropoulos, Zhe Wang, Roxanne Morris, Gene Porter, Gautam Agnihotri, Padmini Salgame, Sean Ekins, Kyu Y Rhee, Nancy Connell, Véronique Dartois, Matthew B Neiditch, Joel S Freundlich, David Alland
We report GSK3011724A (DG167) as a binary inhibitor of β-ketoacyl-ACP synthase (KasA) in Mycobacterium tuberculosis Genetic and biochemical studies established KasA as the primary target. The X-ray crystal structure of the KasA-DG167 complex refined to 2.0-Å resolution revealed two interacting DG167 molecules occupying nonidentical sites in the substrate-binding channel of KasA. The binding affinities of KasA to DG167 and its analog, 5g, which binds only once in the substrate-binding channel, were determined, along with the KasA-5g X-ray crystal structure...
December 18, 2018: MBio
https://read.qxmd.com/read/30545003/optimization-and-validation-of-a-chromatographic-method-for-the-quantification-of-isoniazid-in-urine-of-tuberculosis-patients-according-to-the-european-medicines-agency-guideline
#7
Pooja Mishra, Jaume Albiol-Chiva, Devasish Bose, Abhilasha Durgbanshi, Juan Peris-Vicente, Samuel Carda-Broch, Josep Esteve-Romero
Isoniazid is a drug that is widely used against tuberculosis. However, it shows high interpatient variability in metabolism kinetics and clinical effect, which complicates the prescription of the medication and jeopardizes the success of the therapy. Therefore, in a specific patient, the pharmacokinetics of the drug must be elucidated to decide the proper dosage and intake frequency to make the drug suitable for therapeutic drug monitoring. This can be performed by the quantification of the drug in urine as this process is non-invasive and allows the effects of long-time exposure to be inferred...
December 11, 2018: Antibiotics
https://read.qxmd.com/read/30501530/current-research-towards-optimizing-dosing-of-first-line-antituberculosis-treatment
#8
Helen McIlleron, Maxwell T Chirehwa
Drug concentrations in tuberculosis patients on standard regimens vary widely with clinically important consequences. Areas covered: We review the available literature identifying factors correlated with pharmacokinetic variability of antituberculosis drugs. Based on population pharmacokinetic models and the weight, height and sex distributions in a large data base of African tuberculosis patients, we propose simplified weight-based doses of the available fixed dose combination(FDC) for adults with drug susceptible tuberculosis...
December 1, 2018: Expert Review of Anti-infective Therapy
https://read.qxmd.com/read/30496465/efficacy-versus-hepatotoxicity-of-high-dose-rifampin-pyrazinamide-and-moxifloxacin-to-shorten-tuberculosis-therapy-duration-there-is-still-fight-in-the-old-warriors-yet
#9
Shashikant Srivastava, Devyani Deshpande, Gesham Magombedze, Tawanda Gumbo
Background: One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity. Methods: We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg/day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB)...
November 28, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://read.qxmd.com/read/30496457/ethionamide-pharmacokinetics-pharmacodynamics-derived-dose-the-role-of-mics-in-clinical-outcome-and-the-resistance-arrow-of-time-in-multidrug-resistant-tuberculosis
#10
Devyani Deshpande, Jotam G Pasipanodya, Stellah G Mpagama, Shashikant Srivastava, Paula Bendet, Thearith Koeuth, Pooi S Lee, Scott K Heysell, Tawanda Gumbo
Background: Ethionamide is used to treat multidrug-resistant tuberculosis (MDR-TB). The antimicrobial pharmacokinetics/pharmacodynamics, the contribution of ethionamide to the multidrug regimen, and events that lead to acquired drug resistance (ADR) are unclear. Methods: We performed a multidose hollow fiber system model of tuberculosis (HFS-TB) study to identify the 0-24 hour area under the concentration-time curve (AUC0-24) to minimum inhibitory concentration (MIC) ratios that achieved maximal kill and ADR suppression, defined as target exposures...
November 28, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://read.qxmd.com/read/30474434/intensified-antibiotic-treatment-of-tuberculosis-meningitis
#11
Fiona V Cresswell, Lindsey Te Brake, Rachel Atherton, Rovina Ruslami, Kelly E Dooley, Rob Aarnoutse, Reinout Van Crevel
Meningitis is the most severe manifestation of tuberculosis, resulting in death or disability in over 50% of those affected, with even higher morbidity and mortality among patients with HIV or drug resistance. Antimicrobial treatment of Tuberculous meningitis (TBM) is similar to treatment of pulmonary tuberculosis, although some drugs show poor central nervous system penetration. Therefore, intensification of antibiotic treatment may improve TBM treatment outcomes. Areas covered: In this review, we address three main areas: available data for old and new anti-tuberculous agents; intensified treatment in specific patient groups like HIV co-infection, drug-resistance, and children; and optimal research strategies...
November 24, 2018: Expert Review of Clinical Pharmacology
https://read.qxmd.com/read/30412245/intra-individual-effects-of-food-upon-the-pharmacokinetics-of-rifampicin-and-isoniazid
#12
Ana Requena-Méndez, Geraint Davies, David Waterhouse, Alison Ardrey, Oswaldo Jave, Sonia Llanet López-Romero, Stephen A Ward, David A J Moore
Background: Poor response to TB therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic parameters can be affected by comorbidities or the interaction of drugs with food. Objectives: This study aimed to determine the effect of food intake upon pharmacokinetics of rifampicin and isoniazid in a Peruvian population with TB. Methods: Rifampicin and isoniazid levels were analysed at 2, 4 and 6 h after drug intake in both fasting and non-fasting states using LC-MS methods...
November 8, 2018: Journal of Antimicrobial Chemotherapy
https://read.qxmd.com/read/30406475/a-systematic-review-on-the-effect-of-hiv-infection-on-the-pharmacokinetics-of-first-line-tuberculosis-drugs
#13
REVIEW
Alper Daskapan, Lusiana R Idrus, Maarten J Postma, Bob Wilffert, Jos G W Kosterink, Ymkje Stienstra, Daniel J Touw, Aase B Andersen, Adrie Bekker, Paolo Denti, Agibothu K Hemanth Kumar, Kidola Jeremiah, Awewura Kwara, Helen McIlleron, Graeme Meintjes, Joep J van Oosterhout, Geetha Ramachandran, Neesha Rockwood, Robert J Wilkinson, Tjip S van der Werf, Jan-Willem C Alffenaar
INTRODUCTION: Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK). OBJECTIVES: The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature. METHODS: Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs...
November 8, 2018: Clinical Pharmacokinetics
https://read.qxmd.com/read/30397066/effect-of-rifampin-isoniazid-containing-antituberculosis-therapy-on-efavirenz-pharmacokinetics-in-hiv-infected-children-aged-3-to-14-years-old
#14
Awewura Kwara, Hongmei Yang, Sampson Antwi, Anthony Enimil, Fizza S Gillani, Albert Dompreh, Antoinette Ortsin, Theresa Opoku, Dennis Bosomtwe, Anima Sarfo, Lubbe Wiesner, Jennifer Norman, Wael A Alghamdi, Taimour Langaee, Charles A Peloquin, Michael H Court, David J Greenblatt
We compared efavirenz pharmacokinetic (PK) parameters in children with TB/HIV coinfection on and off first-line antituberculosis therapy to that in HIV-infected children. Children aged 3 to 14 years old with HIV infection with and without TB were treated with standard efavirenz-based antiretroviral therapy without any efavirenz dose adjustments. The new World Health Organization recommended antituberculosis drugs dosages were used in the co-infected participants. Steady-state efavirenz concentrations after 4 weeks of antiretroviral therapy were measured using validated LC/MS/MS assays...
November 5, 2018: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/30296686/design-synthesis-and-anti-mycobacterial-activity-evaluation-of-benzofuran-isatin-hybrids
#15
Feng Gao, Hua Yang, Tianyu Lu, Zijian Chen, Long Ma, Zhi Xu, Paul Schaffer, Guangming Lu
Herein we report the design and synthesis of a series of novel benzofuran-isatin hybrids, and in vitro evaluation of their anti-mycobacterial activity against both drug-susceptible and multi-drug resistant (MDR) Mycobacterium tuberculosis (MTB) strains. In parallel, cytotoxicity of these hybrids was also tested in VERO cells. Preliminary results indicated that all hybrids with acceptable cytotoxicity in VERO cells (CC50 : 128->1024 μg/mL) exhibited considerable anti-mycobacterial activities against MTB H37 Rv and MDR-TB with MIC ranging from 0...
November 5, 2018: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30239829/effect-of-efavirenz-based-antiretroviral-therapy-and-high-dose-rifampicin-on-the-pharmacokinetics-of-isoniazid-and-acetyl-isoniazid
#16
Maxwell T Chirehwa, Helen McIlleron, Lubbe Wiesner, Dissou Affolabi, Oumou Bah-Sow, Corinne Merle, Paolo Denti
Objectives: To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of isoniazid and acetyl-isoniazid. Methods: TB/HIV-coinfected patients participating in the three-treatment-arm RAFA randomized controlled trial conducted in West Africa were recruited into the pharmacokinetics sub-study. Five serial blood samples were collected on a single visit between 4 and 8 weeks after initiation of antituberculosis treatment...
September 18, 2018: Journal of Antimicrobial Chemotherapy
https://read.qxmd.com/read/30126955/effect-of-diabetes-mellitus-on-the-pharmacokinetics-and-pharmacodynamics-of-tuberculosis-treatment
#17
Omamah Alfarisi, Vidya Mave, Sanjay Gaikwad, Tushar Sahasrabudhe, Geetha Ramachandran, Hemanth Kumar, Nikhil Gupte, Vandana Kulkarni, Sona Deshmukh, Sachin Atre, Swapnil Raskar, Rahul Lokhande, Madhusudan Barthwal, Arjun Kakrani, Sandy Chon, Amita Gupta, Jonathan E Golub, Kelly E Dooley
Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized. Newly diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (predose and 0.5, 2, and 6 h postdose) during the intensive and continuation phases of treatment...
November 2018: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/30124844/distribution-of-plasma-concentrations-of-first-line-anti-tb-drugs-and-individual-mics-a-prospective-cohort-study-in-a-low-endemic-setting
#18
Katarina Niward, Lina Davies Forsman, Judith Bruchfeld, Erja Chryssanthou, Oskar Carlström, Teba Alomari, Björn Carlsson, Anton Pohanka, Mikael Mansjö, Michaela Jonsson Nordvall, Anders G Johansson, Erik Eliasson, Jim Werngren, Jakob Paues, Ulrika S H Simonsson, Thomas Schön
Background: Therapeutic drug monitoring (TDM) could improve current TB treatment, but few studies have reported pharmacokinetic data together with MICs. Objectives: To investigate plasma concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol along with MICs. Methods: Drug concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol were analysed pre-dose and 2, 4 and 6 h after drug intake at week 2 in 31 TB patients and MICs in BACTEC 960 MGIT were determined at baseline...
August 14, 2018: Journal of Antimicrobial Chemotherapy
https://read.qxmd.com/read/30084943/pharmacokinetics-of-efavirenz-400-mg-once-daily-coadministered-with-isoniazid-and-rifampicin-in-human-immunodeficiency-virus-infected-individuals
#19
Maddalena Cerrone, Xinzhu Wang, Megan Neary, Christine Weaver, Serge Fedele, Isaac Day-Weber, Andrew Owen, Andrew Hill, Myra McClure, Marta Boffito
Background: The World Health Organization recommends efavirenz 400 mg (EFV400) as first-line antiretroviral therapy, with a disclaimer that no data with anti-tuberculosis (TB) treatment exist. Many people living with human immunodeficiency virus (PLWH) require TB treatment with isoniazid (INH) and rifampicin (RIF), which affect cytochrome P450 and antiretroviral exposure. Methods: PLWH receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/EFV 600 mg with a viral load (VL) <50 copies/mL switched to TDF/FTC/EFV400...
August 6, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://read.qxmd.com/read/30025351/design-synthesis-and-antimicrobial-evaluation-of-propylene-tethered-ciprofloxacin-isatin-hybrids
#20
Ruo Wang, Xueyang Yin, Yaohuan Zhang, Weitao Yan
Twelve novel propylene-tethered ciprofloxacin-isatin hybrids 3a-f and 4a-f were designed, synthesized and characterized by MS, HRMS, 1 H NMR and 13 C NMR. All hybrids were evaluated for their in vitro antimicrobial activities against representative Gram-positive, Gram-negative and mycobacterial pathogens, cytotoxicity in VERO cell line as well as metabolic stability and in vivo pharmacokinetic (PK) properties. The preliminary results indicated that all mono-isatin-ciprofloxacin hybrids exhibited excellent antibacterial activities with MIC ranging from ≤0...
August 5, 2018: European Journal of Medicinal Chemistry
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