ArticleAntimicrobial agents and chemotherapy2014
Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability.
Article 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 2 registered trials, which are not on this map. Cited by 23 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.
Phase I Dose Escalation Study of the Pharmacokinetics, Safety and Tolerability of Rifapentine and the Effects of Increasing Doses of Rifapentine on Induction of Metabolizing Enzymes in Healthy Volunteers
TBTC Study 31 PK/PD: Population Pharmacokinetic and Pharmacodynamic Study of Efficacy and Safety of High-Dose Rifapentine and Moxifloxacin for Treatment of Tuberculosis in the Study 31 Treatment Trial: Intensive PK Sampling
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.American journal of respiratory and critical care medicine · 2020Pooled it
- Bridging to Paediatric Dosing: Relative Bioavailability of Suspended Rifapentine and Isoniazid in an Open-Label Randomized Trial in Adults on Tuberculosis Preventive Therapy.Clinical pharmacokinetics · 2025Trial
- Population Pharmacokinetic Modeling and Simulation of Rifapentine Supports Concomitant Antiretroviral Therapy with Efavirenz and Non-Weight Based Dosing.Antimicrobial agents and chemotherapy · 2022Trial
- Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.Antimicrobial agents and chemotherapy · 2019Trial
- Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.Clinical pharmacology and therapeutics · 2017Trial
- Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.American journal of respiratory and critical care medicine · 2015Trial
- Article
- Conjugated hyperbilirubinemia associated with accidental rifapentine overdose.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2024Article
- Comparative study on the bioavailability and bioequivalence of rifapentine capsules in humans.Frontiers in pharmacology · 2024Article
- An Overview of Various Rifampicin Analogs againstMedicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Optimizing (O) rifapentine-based (RI) regimen and shortening (EN) the treatment of drug-susceptible tuberculosis (T) (ORIENT) using an adaptive seamless design: study protocol of a multicenter randomized controlled trial.BMC infectious diseases · 2023Article
- An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.Clinical pharmacology and therapeutics · 2022Article
- Evaluation of drug-drug interaction between rilpivirine and rifapentine using PBPK modelling.Frontiers in pharmacology · 2022Article
- Comparative Efficacy of Rifapentine Alone and in Combination with Isoniazid for Latent Tuberculosis Infection: a Translational Pharmacokinetic-Pharmacodynamic Modeling Study.Antimicrobial agents and chemotherapy · 2021Article
- Increased bactericidal activity but dose-limiting intolerability at 50 mg·kgThe European respiratory journal · 2021Article
- A Pharmacology Perspective of Simultaneous Tuberculosis and Hepatitis C Treatment.Antimicrobial agents and chemotherapy · 2019Review
- High-Dose Rifamycins Enable Shorter Oral Treatment in a Murine Model of Mycobacterium ulcerans Disease.Antimicrobial agents and chemotherapy · 2019Article
- Modeling and Simulation of Pretomanid Pharmacokinetics in Pulmonary Tuberculosis Patients.Antimicrobial agents and chemotherapy · 2018Article
- Clinical and pharmacological hallmarks of rifapentine's use in diabetes patients with active and latent tuberculosis: do we know enough?Drug design, development and therapy · 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
8 authors at 6 institutions in 1 country.
Funding
Abstract
Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters · h(-1), respectively, after a single dose to 2.2 and 5.0 liters · h(-1), respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01162486.).
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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.