Trial reportAntimicrobial agents and chemotherapy2009
Assessment of the effects of the nitroimidazo-oxazine PA-824 on renal function in healthy subjects.
Trial report in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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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
27 citing papers in PubMed, 58 citations in OpenAlex.
- 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 dose selection for pulmonary tuberculosis: An application of multi-objective optimization to dosage regimen design.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Effect of a high-calorie, high-fat meal on the bioavailability and pharmacokinetics of PA-824 in healthy adult subjects.Antimicrobial agents and chemotherapy · 2013Trial
- A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects.British journal of clinical pharmacology · 2013Trial
- Early bactericidal activity and pharmacokinetics of PA-824 in smear-positive tuberculosis patients.Antimicrobial agents and chemotherapy · 2010Trial
- Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects.Antimicrobial agents and chemotherapy · 2009Trial
- Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations.Microorganisms · 2026Review
- Article
- Pharmacology of emerging drugs for the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Review
- Pretomanid for tuberculosis treatment: an update for clinical purposes.Current research in pharmacology and drug discovery · 2022Review
- Profiling Pretomanid as a Therapeutic Option for TB Infection: Evidence to Date.Drug design, development and therapy · 2021Review
- An Exposure-Response Perspective on the Clinical Dose of Pretomanid.Antimicrobial agents and chemotherapy · 2020Article
- Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020Review
- Population Pharmacokinetics of the Antituberculosis Agent Pretomanid.Antimicrobial agents and chemotherapy · 2019Article
- Modeling and Simulation of Pretomanid Pharmacodynamics in Pulmonary Tuberculosis Patients.Antimicrobial agents and chemotherapy · 2019Article
- Modeling and Simulation of Pretomanid Pharmacokinetics in Pulmonary Tuberculosis Patients.Antimicrobial agents and chemotherapy · 2018Article
- Investigational drugs for visceral leishmaniasis.Expert opinion on investigational drugs · 2015Article
- Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.Kidney international · 2014Article
- Evaluation of pharmacokinetic interaction between PA-824 and midazolam in healthy adult subjects.Antimicrobial agents and chemotherapy · 2013Article
- Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism underlying a dose-dependent, reversible increase in serum creatinine (SC) caused by the administration of PA-824, a novel nitroimidazo-oxazine, was evaluated in 47 healthy male and female volunteers. Subjects were administered either 800 or 1,000 mg PA-824 or matching placebo once daily for 8 days. The following renal function parameters were determined before and during dosing and after a 7-day washout: SC, glomerular filtration rate (GFR; measured as the iohexol clearance), effective renal plasma flow (ERPF; measured as the para-amino hippurate clearance), filtration fraction (FF), creatinine clearance (CrCl), extraglomerular creatinine excretion (EGCE; defined as CrCl minus GFR), blood urea nitrogen (BUN), and uric acid (UA) levels. Eight days' administration of 800 or 1,000 mg PA-824 was associated with increased SC and a trend toward decreased CrCl and EGCE. SC, CrCl, and EGCE values returned to normal/baseline within 1 week's washout. GFR, ERPF, FF, BUN, and UA values were similar across groups during treatment and washout. The reversible increase in SC observed in this and earlier trials of PA-824, thus, did not appear to be the result of a pathological effect on renal function (as measured by GFR, ERPF, FF, BUN, or UA). Pharmacokinetic analyses confirmed that PA-824 exposures were similar to those in previous healthy-volunteer clinical studies. That EGCE declined maximally when drug levels were highest suggests that PA-824 causes creatinine levels to rise by inhibiting renal tubular creatinine secretion. Such an effect, considered clinically benign, has been described for several marketed drugs.
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