SynthesisAntimicrobial agents and chemotherapy2010
Clinical and toxicodynamic evidence that high-dose pyrazinamide is not more hepatotoxic than the low doses currently used.
Synthesis in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Guideline
- Pyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized Controlled Clinical Trial.American journal of respiratory and critical care medicine · 2024Trial
- Optimising pyrazinamide for the treatment of tuberculosis.The European respiratory journal · 2021Trial
- Pyrazinamide-induced hepatotoxicity mediated by aldehyde oxidase and xanthine oxidase.Archives of toxicology · 2026Article
- A novel machine-learning based optimization: identifying new treatment regimens for tuberculosis.Numerical algebra, control and optimization · 2025Article
- A scoping review of interventions to prevent and treat adverse events during treatment of rifampin-susceptible tuberculosis.PloS one · 2025Article
- A Balancing Act: Finding the Right Dose of Pyrazinamide to Treat Tuberculosis.American journal of respiratory and critical care medicine · 2024Article
- Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Article
- Is the Pharmacokinetics of First-Line Anti-TB Drugs a Cause of High Mortality Rates in TB Patients Admitted to the ICU? A Non-Compartmental Pharmacokinetic Analysis.Tropical medicine and infectious disease · 2023Article
- Optimizing tuberculosis treatment efficacy: Comparing the standard regimen with Moxifloxacin-containing regimens.PLoS computational biology · 2023Article
- Development of a population pharmacokinetic model of pyrazinamide to guide personalized therapy: impacts of geriatric and diabetes mellitus on clearance.Frontiers in pharmacology · 2023Article
- Diagnostic Accuracy of Therapeutic Drug Monitoring During Tuberculosis Treatment.Journal of clinical pharmacology · 2022Article
- Population Pharmacokinetic Modelling and Limited Sampling Strategies for Therapeutic Drug Monitoring of Pyrazinamide in Patients with Tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Article
- Drug exposure and susceptibility of second-line drugs correlate with treatment response in patients with multidrug-resistant tuberculosis: a multicentre prospective cohort study in China.The European respiratory journal · 2022Article
- Population Pharmacokinetics and Significant Under-Dosing of Anti-Tuberculosis Medications in People with HIV and Critical Illness.Antibiotics (Basel, Switzerland) · 2021Article
- Factors Affecting the Pharmacokinetics of Pyrazinamide and Its Metabolites in Patients Coinfected with HIV and Implications for Individualized Dosing.Antimicrobial agents and chemotherapy · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- The impact of inclusion, dose and duration of pyrazinamide (PZA) on efficacy and safety outcomes in tuberculosis: systematic review and meta-analysis protocol.Systematic reviews · 2019Article
- The importance of clinical pharmacokinetic-pharmacodynamic studies in unraveling the determinants of early and late tuberculosis outcomes.International journal of pharmacokinetics · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Antimicrobial pharmacokinetic-pharmacodynamic studies suggest that pyrazinamide doses higher than those currently recommended may be more efficacious. However, high pyrazinamide doses are believed to be hepatotoxic. Searches for clinical trials in MEDLINE, EBSCOHOST, and the Cochrane Controlled Trial Register were made. Studies that employed pyrazinamide dose scheduling and pharmacokinetic analysis design were examined. Population pharmacokinetic modeling methods were utilized to identify parameters associated with toxicity. At an equivalent area under the concentration-time curve, the time that concentration persisted above some thresholds was associated with overall adverse events (P = 0.032), arthralgia (P = 0.089), and an elevated serum aspartate aminotransferase level at 3 months (P = 0.067). Next, a meta-analysis was utilized to compare rates of adverse events (i) between different pyrazinamide doses, (ii) between different dosing schedules, and (iii) between pyrazinamide-containing and non-pyrazinamide-containing antituberculosis regimens. The 29 studies selected were heterogeneous (Cochrane Q statistic P value of <0.001; I(2) of >95%). For the once-a-day dosing schedule, arthralgia was dose dependent (r(2) = 0.996). However, arthralgia was less common with intermittent dosing, consistent with the time concentration persisted above the threshold. Arthralgia was generally clinically inconsequential. The frequencies of hepatotoxicity were 0.057 (95% confidence interval [CI], 0.021 to 0.141) for pyrazinamide monotherapy, 0.044 (CI, 0.033 to 0.059) for pyrazinamide-containing combination regimens, and 0.040 (CI, 0.023 to 0.040) for non-pyrazinamide-containing combination regimens. The frequencies of hepatotoxicity were 0.042 (CI, 0.026 to 0.067) for 30 mg/kg of body weight, 0.055 (CI, 0.031 to 0.094) at 40 mg/kg, and 0.098 (CI, 0.047 to 0.193) at 60 mg/kg of pyrazinamide. Thus, high-dose pyrazinamide did not significantly increase hepatotoxicity. This suggests that a considerable portion of hepatotoxicity rates may be idiosyncratic.
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.