ArticleAntimicrobial agents and chemotherapy2009
Population modeling and Monte Carlo simulation study of the pharmacokinetics and antituberculosis pharmacodynamics of rifampin in lungs.
Article 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 54 papers.
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Who cites it
54 citing papers in PubMed, 102 citations in OpenAlex.
- Assessment of body mass-related covariates for rifampicin pharmacokinetics in healthy Caucasian volunteers.European journal of clinical pharmacology · 2024Trial
- Population pharmacokinetics of gentamicin in haemodialysis patients: modelling, simulations and recommendations.European journal of clinical pharmacology · 2020Trial
- Population pharmacokinetics and pharmacodynamics of teicoplanin in neonates: making better use of C-reactive protein to deliver individualized therapy.The Journal of antimicrobial chemotherapy · 2016Trial
- Population pharmacokinetics of nevirapine in Malaysian HIV patients: a non-parametric approach.European journal of clinical pharmacology · 2016Trial
- A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells--using rifampicin as an example.European journal of clinical pharmacology · 2015Trial
- Falling short: Inadequate target attainment in guideline-based therapy of nontuberculous mycobacterial disease.medRxiv : the preprint server for health sciences · 2026Article
- Defining Optimal Sampling Strategies for Cefepime Model-Informed Precision Dosing.Therapeutic drug monitoring · 2026Article
- A Nonparametric Population Pharmacokinetic Model of Selumetinib in Pediatric Patients Diagnosed With Neurofibromatosis-I or Plexiform Neurofibromas.CPT: pharmacometrics & systems pharmacology · 2026Article
- Population pharmacokinetics of meropenem-vaborbactam in acutely ill hospitalized patients with various degrees of renal dysfunction including continuous renal replacement therapy.Antimicrobial agents and chemotherapy · 2025Article
- Individual meropenem epithelial lining fluid and plasma PK/PD target attainment.Antimicrobial agents and chemotherapy · 2023Article
- A Comparison of Methods to Estimate Additive-by-Additive-by-Additive of QTL×QTL×QTL Interaction Effects by Monte Carlo Simulation Studies.International journal of molecular sciences · 2023Article
- Pharmacokinetic study of high-dose oral rifampicin in critically Ill patients with multidrug-resistant Acinetobacter baumannii infection.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022Article
- Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review-Part II.Antibiotics (Basel, Switzerland) · 2022Review
- Inhalable Mannosylated Rifampicin-Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy.Pharmaceutics · 2022Article
- L-GSH Supplementation in Conjunction With Rifampicin Augments the Treatment Response toFrontiers in pharmacology · 2022Article
- Intracellular Accumulation of Novel and Clinically Used TB Drugs Potentiates Intracellular Synergy.Microbiology spectrum · 2021Article
- Population Pharmacokinetic Modeling and Dosing Simulations of Tobramycin in Pediatric Patients with Cystic Fibrosis.Antimicrobial agents and chemotherapy · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Population Pharmacokinetics of Piperacillin in Non-Critically Ill Patients with Bacteremia Caused by Enterobacteriaceae.Antibiotics (Basel, Switzerland) · 2021Article
- Optimizing Aminoglycoside Dosing Regimens for Critically Ill Pediatric Patients with Augmented Renal Clearance: a Convergence of Parametric and Nonparametric Population Approaches.Antimicrobial agents and chemotherapy · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Little information exists on the pulmonary pharmacology of antituberculosis drugs. We used population pharmacokinetic modeling and Monte Carlo simulation to describe and explore the pulmonary pharmacokinetics and pharmacodynamics of rifampin (RIF; rifampicin). A population pharmacokinetic model that adequately described the plasma, epithelial lining fluid (ELF), and alveolar cell (AC) concentrations of RIF in a population of 34 human volunteers was made by use of the nonparametric adaptive grid (NPAG) algorithm. The estimated concentrations correlated well with the measured concentrations, and there was little bias and good precision. The results obtained with the NPAG algorithm were then imported into Matlab software to perform a 10,000-subject Monte Carlo simulation. The ability of RIF to suppress the development of drug resistance and to induce a sufficient bactericidal effect against Mycobacterium tuberculosis was evaluated by calculating the proportion of subjects achieving specific target values for the maximum concentration of drug (C(max))/MIC ratio and the area under the concentration-time curve from time zero to 24 h (AUC(0-24))/MIC ratio, respectively. At the lowest MIC (0.01 mg/liter), after the administration of one 600-mg oral dose, the rates of target attainment for C(max)/MIC (> or =175) were 95% in ACs, 48.8% in plasma, and 35.9% in ELF. Under the same conditions, the target attainment results for the killing effect were 100% in plasma (AUC(0-24)/MIC > or = 271) but only 54.5% in ELF (AUC(0-24)/MIC > or = 665). The use of a 1,200-mg RIF dose was associated with better results for target attainment. The overall results suggest that the pulmonary concentrations obtained with the standard RIF dose are too low in most subjects. This work supports the need to evaluate higher doses of RIF for the treatment of patients with tuberculosis.
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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.