ArticleAntimicrobial agents and chemotherapy2003
In vivo pharmacokinetics and pharmacodynamics of a new triazole, voriconazole, in a murine candidiasis model.
Article in Antimicrobial agents and chemotherapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Observational study of the clinical efficacy of voriconazole and its relationship to plasma concentrations in patients.Antimicrobial agents and chemotherapy · 2011Pooled it
- Antifungal pharmacodynamics: Latin America's perspective.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesPooled it
- Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial.The Journal of antimicrobial chemotherapy · 2016Trial
- Achieving target voriconazole concentrations more accurately in children and adolescents.Antimicrobial agents and chemotherapy · 2015Trial
- Integrated population pharmacokinetic analysis of voriconazole in children, adolescents, and adults.Antimicrobial agents and chemotherapy · 2012Trial
- Steady-state plasma pharmacokinetics of oral voriconazole in obese adults.Antimicrobial agents and chemotherapy · 2011Trial
- Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods.Antimicrobial agents and chemotherapy · 2007Trial
- Correlation of MIC with outcome for Candida species tested against voriconazole: analysis and proposal for interpretive breakpoints.Journal of clinical microbiology · 2006Trial
- Fluconazole MIC and the fluconazole dose/MIC ratio correlate with therapeutic response among patients with candidemia.Antimicrobial agents and chemotherapy · 2005Trial
- Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration.Antimicrobial agents and chemotherapy · 2004Trial
- Toward Genotype-Informed Dosing of Voriconazole: Head-to-Head Simulations Across CYP2C19 Phenotypes Using Population Pharmacokinetic Models.Pharmaceutics · 2025Article
- Voriconazole therapeutic drug monitoring including analysis of CYP2C19 phenotype in immunocompromised pediatric patients with invasive fungal infections.European journal of clinical pharmacology · 2024Article
- Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antifungal Agents: A Review.Clinical pharmacokinetics · 2024Review
- Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.Antimicrobial agents and chemotherapy · 2022Article
- Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies.Pharmaceutics · 2021Review
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- The Role of New Posaconazole Formulations in the Treatment of Candida albicans Infections: Data from anAntimicrobial agents and chemotherapy · 2021Article
- Does DDI-Predictor Help Pharmacists to Detect Drug-Drug Interactions and Resolve Medication Issues More Effectively?Metabolites · 2021Article
- Predicting the Outcome of Voriconazole Individualized Medication Using Integrated Pharmacokinetic/Pharmacodynamic Model.Frontiers in pharmacology · 2021Article
- Contribution of Population Pharmacokinetics of Glycopeptides and Antifungals to Dosage Adaptation in Paediatric Onco-hematological Malignancies: A Review.Frontiers in pharmacology · 2021Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vivo studies have described the pharmacodynamic (PD) characteristics of several triazoles. These investigations have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic (PK)-PD parameter associated with treatment efficacy. Further analyses from these in vivo studies have demonstrated that a triazole free drug 24-h AUC/MIC of 20 to 25 is predictive of treatment success. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the PK-PD of the new triazole voriconazole. PK and PD parameters (percentage of time that the concentration remains above the MIC [T > MIC], AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by the organism number in kidney cultures after 24 h of therapy. Voriconazole kinetics and protein binding were studied in infected neutropenic mice. Peak level/dose and AUC/dose values ranged from 0.1 to 0.2 and 0.1 to 0.7, respectively. The serum elimination half-life ranged from 0.7 to 2.9 h. The level of protein binding in mouse serum was 78%. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (R(2) for AUC/MIC ratio = 82%, R(2) for peak level/MIC ratio = 63%, R(2) for T > MIC = 75%). Similar studies were conducted with nine additional C. albicans isolates with various voriconazole susceptibilities (MICs, 0.007 to 0.25 micro g/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The voriconazole free drug AUC/MIC ratios were similar for all of the organisms studied (range, 11 to 58; mean +/- standard deviation, 24 +/- 17 [P = 0.45]). These AUC/MIC ratios observed for free drug are similar to those observed for other triazoles in this model.
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