ArticleBritish journal of clinical pharmacology2007
A d-optimal designed population pharmacokinetic study of oral itraconazole in adult cystic fibrosis patients.
Article in British journal of clinical pharmacology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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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Who cites it
13 citing papers in PubMed, 47 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of Fosravuconazole, Itraconazole, and Hydroxyitraconazole in Sudanese Patients With Eumycetoma.The Journal of infectious diseases · 2025Trial
- Population pharmacokinetic modeling of itraconazole and hydroxyitraconazole for oral SUBA-itraconazole and sporanox capsule formulations in healthy subjects in fed and fasted states.Antimicrobial agents and chemotherapy · 2015Trial
- CF Fungal Disease in the Age of CFTR Modulators.Mycopathologia · 2021Review
- Significant elevation of free itraconazole concentration at onset of adverse effects: A case report.Clinical case reports · 2021Article
- Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children.Clinical pharmacokinetics · 2019Article
- Population in vitro-in vivo pharmacokinetic model of first-pass metabolism: itraconazole and hydroxy-itraconazole.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Optimal sampling of antipsychotic medicines: a pharmacometric approach for clinical practice.British journal of clinical pharmacology · 2014Article
- Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria.Malaria journal · 2012Article
- Interpreting population pharmacokinetic-pharmacodynamic analyses - a clinical viewpoint.British journal of clinical pharmacology · 2011Review
- Pharmacokinetic design optimization in children and estimation of maturation parameters: example of cytochrome P450 3A4.Journal of pharmacokinetics and pharmacodynamics · 2011Article
- Semi-mechanistic population pharmacokinetic drug-drug interaction modelling of a long half-life substrate and itraconazole.Clinical pharmacokinetics · 2010Article
- Penetration of antibacterials into bone: pharmacokinetic, pharmacodynamic and bioanalytical considerations.Clinical pharmacokinetics · 2009Review
- Development of a sufficient design for estimation of fluconazole pharmacokinetics in people with HIV infection.British journal of clinical pharmacology · 2008Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe primary objective of the study was to estimate the population pharmacokinetic parameters for itraconazole and hydroxy-itraconazole, in particular, the relative oral bioavailability of the capsule compared with solution in adult cystic fibrosis patients, in order to develop new dosing guidelines. A secondary objective was to evaluate the performance of a population optimal design.
methodsThe blood sampling times for the population study were optimized previously using POPT v.2.0. The design was based on the administration of solution and capsules to 30 patients in a cross-over study. Prior information suggested that itraconazole is generally well described by a two-compartment disposition model with either linear or saturable elimination. The pharmacokinetics of itraconazole and the metabolite were modelled simultaneously using NONMEM. Dosing schedules were simulated to assess their ability to achieve a trough target concentration of 0.5 mg ml(-1).
resultsOut of 241 blood samples, 94% were taken within the defined optimal sampling windows. A two-compartment model with first order absorption and elimination best described itraconazole kinetics, with first order metabolism to the hydroxy-metabolite. For itraconazole the absorption rate constants (between-subject variability) for capsule and solution were 0.0315 h(-1) (91.9%) and 0.125 h(-1) (106.3%), respectively, and the relative bioavailability of the capsule was 0.82 (62.3%) (confidence interval 0.36, 1.97), compared with the solution. There was no evidence of nonlinearity. Simulations from the final model showed that a dosing schedule of 500 mg twice daily for both formulations provided the highest chance of target success.
conclusionThe optimal design performed well and the pharmacokinetics of itraconazole and hydroxy-itraconazole were described adequately by the model. The relative bioavailability for itraconazole capsules was 82% compared with the solution.
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