Trial reportAntimicrobial agents and chemotherapy2014
Phase I safety, pharmacokinetics, and pharmacogenetics study of the antituberculosis drug PA-824 with concomitant lopinavir-ritonavir, efavirenz, or rifampin.
Trial report in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01571414 (A Phase I, Three-Arm Safety, Tolerability, and Pharmacokinetic Interaction Study of PA-824, an Investigational Nitroimidazole for the Treatment of Tuberculosis, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin), which is not on this map. Cited by 32 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.
A Phase I, Three-Arm Safety, Tolerability, and Pharmacokinetic Interaction Study of PA-824, an Investigational Nitroimidazole for the Treatment of Tuberculosis, Together With Efavirenz, Ritonavir-Boosted Lopinavir, or Rifampin
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Population pharmacokinetics and target attainment of pretomanid in rifampicin-resistant tuberculosis patients.Scientific reports · 2026Trial
- Assessing Pretomanid for Tuberculosis (APT), a Randomized Phase 2 Trial of Pretomanid-Containing Regimens for Drug-Sensitive Tuberculosis: 12-Week Results.American journal of respiratory and critical care medicine · 2023Trial
- Phase 1 Study of the Effects of the Tuberculosis Treatment Pretomanid, Alone and in Combination With Moxifloxacin, on the QTc Interval in Healthy Volunteers.Clinical pharmacology in drug development · 2021Trial
- Pretomanid Pharmacokinetics in the Presence of Rifamycins: Interim Results from a Randomized Trial among Patients with Tuberculosis.Antimicrobial agents and chemotherapy · 2021Trial
- Delamanid Coadministered with Antiretroviral Drugs or Antituberculosis Drugs Shows No Clinically Relevant Drug-Drug Interactions in Healthy Subjects.Antimicrobial agents and chemotherapy · 2016Trial
- Hepatic safety of pretomanid- and pyrazinamide-containing regimens in TB Alliance clinical trials.IJTLD open · 2025Article
- An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens.Current HIV/AIDS reports · 2025Review
- Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Review
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Acceleration of infectious disease drug discovery and development using a humanized model of drug metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Validation and application of a quantitative liquid chromatography tandem mass spectrometry assay for the analysis of rifapentine and 25-O-desacetyl rifapentine in human milk.Journal of pharmaceutical and biomedical analysis · 2022Article
- Delamanid or pretomanid? A Solomonic judgement!The Journal of antimicrobial chemotherapy · 2022Article
- MDR Tuberculosis Treatment.Medicina (Kaunas, Lithuania) · 2022Review
- Pretomanid for tuberculosis treatment: an update for clinical purposes.Current research in pharmacology and drug discovery · 2022Review
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- A validated liquid chromatography tandem mass spectrometry assay for the analysis of pretomanid in plasma samples from pulmonary tuberculosis patients.Journal of pharmaceutical and biomedical analysis · 2021Article
- Profiling Pretomanid as a Therapeutic Option for TB Infection: Evidence to Date.Drug design, development and therapy · 2021Review
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 1 country.
Funding
Abstract
There is an urgent need for new antituberculosis (anti-TB) drugs, including agents that are safe and effective with concomitant antiretrovirals (ARV) and first-line TB drugs. PA-824 is a novel antituberculosis nitroimidazole in late-phase clinical development. Cytochrome P450 (CYP) 3A, which can be induced or inhibited by ARV and antituberculosis drugs, is a minor (∼20%) metabolic pathway for PA-824. In a phase I clinical trial, we characterized interactions between PA-824 and efavirenz (arm 1), lopinavir/ritonavir (arm 2), and rifampin (arm 3) in healthy, HIV-uninfected volunteers without TB disease. Participants in arms 1 and 2 were randomized to receive drugs via sequence 1 (PA-824 alone, washout, ARV, and ARV plus PA-824) or sequence 2 (ARV, ARV with PA-824, washout, and PA-824 alone). In arm 3, participants received PA-824 and then rifampin and then both. Pharmacokinetic sampling occurred at the end of each dosing period. Fifty-two individuals participated. Compared to PA-824 alone, plasma PA-824 values (based on geometric mean ratios) for maximum concentration (Cmax), area under the concentration-time curve from 0 to 24 h (AUC0-24), and trough concentration (Cmin) were reduced 28%, 35%, and 46% with efavirenz, 13%, 17%, and 21% with lopinavir-ritonavir (lopinavir/r) and 53%, 66%, and 85% with rifampin, respectively. Medications were well tolerated. In conclusion, lopinavir/r had minimal effect on PA-824 exposures, supporting PA-824 use with lopinavir/r without dose adjustment. PA-824 exposures, though, were reduced more than expected when given with efavirenz or rifampin. The clinical implications of these reductions will depend upon data from current clinical trials defining PA-824 concentration-effect relationships. (This study has been registered at ClinicalTrials.gov under registration no. NCT01571414.).
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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.