ArticleTuberculosis (Edinburgh, Scotland)2009
A simple in vitro PK/PD model system to determine time-kill curves of drugs against Mycobacteria.
Article in Tuberculosis (Edinburgh, Scotland), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- DynamicAntibiotics (Basel, Switzerland) · 2024Review
- Synthesis, antimycobacterial evaluation, and molecular docking study of 1,2,4-triazole derivatives.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- A 3D-printed multi-compartment device that enables dynamic PK/PD profiles of antibiotics.Analytical and bioanalytical chemistry · 2023Article
- A cell culture system to model pharmacokinetics using adjustable-volume perfused mixing chambers.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- Characterization of spectinamide 1599 efficacy against different mycobacterial phenotypes.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Pharmacodynamic Parameters of Pharmacokinetic/Pharmacodynamic (PK/PD) Integration Models.Frontiers in veterinary science · 2022Review
- Model-Based Exposure-Response Assessment for Spectinamide 1810 in a Mouse Model of Tuberculosis.Antimicrobial agents and chemotherapy · 2021Article
- Anti-tuberculosis effect of isoniazid scales accurately from zebrafish to humans.British journal of pharmacology · 2020Article
- Use of Supplemented or Human Material to Simulate PD Behavior of Antibiotics at the Target Site In Vitro.Pharmaceutics · 2020Review
- Mathematical model and tool to explore shorter multi-drug therapy options for active pulmonary tuberculosis.PLoS computational biology · 2020Article
- Dynamic time-kill curve characterization of spectinamide antibiotics 1445 and 1599 for the treatment of tuberculosis.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Pharmacokinetic/Pharmacodynamic Integration of Doxycycline AgainstFrontiers in pharmacology · 2019Article
- Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies.Pharmaceutics · 2018Article
- A multi-scale approach to designing therapeutics for tuberculosis.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment.Journal of theoretical biology · 2015Article
- Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux.Nature medicine · 2014Article
- PK/PD models in antibacterial development.Current opinion in microbiology · 2013Review
- Clinical pharmacokinetics of antibacterials in cerebrospinal fluid.Clinical pharmacokinetics · 2013Review
- Applications of pharmacometrics in the clinical development and pharmacotherapy of anti-infectives.Expert review of clinical pharmacology · 2013Review
- Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties.Bioorganic & medicinal chemistry · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In vivo tuberculosis is exposed to continually changing drug concentrations for which static minimum inhibitory concentration (MIC) testing may be a poor surrogate. While in vitro approaches to determine time-kill curves for antibiotics have been widely applied in assessing antimicrobial activity against fast growing microorganisms, their availability and application for slow-growing microorganisms including Mycobacterium tuberculosis has so far been scarce. Thus, we developed a novel simple in vitro pharmacokinetic/pharmacodynamic (PK/PD) model for establishing time-kill curves and applied it for evaluating the antimicrobial activity of different dosing regimens of isoniazid (INH) against Mycobacterium bovis BCG as a surrogate for virulent M. tuberculosis. In the in vitro model M. bovis BCG was exposed to INH concentration-time profiles as usually encountered during multiple dose therapy with 25, 100 and 300mg/day in humans who are fast or slow INH metabolizers. Bacterial killing was followed over time by determining viable counts and the resulting time-kill data was analyzed using a semi-mechanistic PK/PD model with an adaptive IC(50) function to describe the emergence of insensitive populations of bacteria over the course of treatment. In agreement with previous studies, the time-kill data suggest that AUC(0-24)/MIC is the PK/PD index that is the most explanatory of the antimicrobial effect of INH. The presented in vitro PK/PD model and associated modeling approach were able to characterize the time-kill kinetics of INH in M. bovis BCG, and may in general serve as a potentially valuable, low cost tool for the assessment of antibacterial activity in slow-growing organisms in drug development and applied pharmacotherapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.