Trial reportBritish journal of clinical pharmacology2008
The different effects of itraconazole on the pharmacokinetics of fexofenadine enantiomers.
Trial report in British journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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.
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Who cites it
11 citing papers in PubMed.
- Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers.European journal of clinical pharmacology · 2014Trial
- Enantioselective disposition of fexofenadine with the P-glycoprotein inhibitor verapamil.British journal of clinical pharmacology · 2009Trial
- Clinical Pharmacokinetics of Fexofenadine: A Systematic Review.Pharmaceutics · 2024Review
- Development of fexofenadine self-microemulsifying delivery systems: an efficient way to improve intestinal permeability.Therapeutic delivery · 2024Article
- Chiral Discrimination of P-glycoprotein in Parturient Women: Effect of Fluoxetine on Maternal-Fetal Fexofenadine Pharmacokinetics.Pharmaceutical research · 2020Article
- A Generic Model for Quantitative Prediction of Interactions Mediated by Efflux Transporters and Cytochromes: Application to P-Glycoprotein and Cytochrome 3A4.Clinical pharmacokinetics · 2019Article
- Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.British journal of clinical pharmacology · 2015Review
- Physiologically based pharmacokinetic modelling and in vivo [I]/K(i) accurately predict P-glycoprotein-mediated drug-drug interactions with dabigatran etexilate.British journal of pharmacology · 2014Article
- The functional influences of common ABCB1 genetic variants on the inhibition of P-glycoprotein by Antrodia cinnamomea extracts.PloS one · 2014Article
- Evaluation of in vivo P-glycoprotein phenotyping probes: a need for validation.Clinical pharmacokinetics · 2010Review
- Update on prescription and over-the-counter histamine inverse agonists in rhinitis therapy.Current allergy and asthma reports · 2009Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
what is already known about this subjectRecently, we have shown that the plasma concentration of R-fexofenadine is greater than that of the S-enantiomer. Although itraconazole co-administration is known to increase the bioavailability of a racemic mixture of fexofenadine, little is known about the stereoselective inhibition of P-gp activity by itraconazole. WHAT THIS STUDY ADDS: This study indicates that the stereoselective pharmacokinetics of fexofenadine are due to P-gp-mediated transport and its stereoselectivity is altered by itraconazole, a an inhibitor of P-gp.
aimsThe aim of this study was to determine the inhibitory effect of itraconazole, a P-glycoprotein (P-gp) inhibitor, on the stereoselective pharmacokinetics of fexofenadine.
methodsA two-way double-blind, placebo-controlled crossover study was performed with a 2-week washout period. Twelve healthy volunteers received either itraconazole 200 mg or matched placebo in a randomized fashion with a single oral dose of fexofenadine 60 mg simultaneously. The plasma concentrations and the amount of urinary excretion (Ae) of fexofenadine enantiomers were measured up to 24 h after dosing.
resultsAfter placebo administration, mean AUC(0,24 h) of S- and R-fexofenadine was 474 ng ml(-1) h (95% CI 311, 638) and 798 ng ml(-1) h (95% CI 497, 1101), respectively. Itraconazole affected the pharmacokinetic parameters of S-fexofenadine more, and increased AUC(0,24 h) of S-fexofenadine and R-fexofenadine by 4.0-fold (95% CI of differences 2.8, 5.3; P < 0.001) and by 3.1-fold (95% CI of differences 2.2, 4.0; P = 0.014), respectively, and Ae(0,24 h) of S-fexofenadine and R-fexofenadine by 3.6-fold (95% CI of differences 2.6, 4.5; P < 0.001) and by 2.9-fold (95% CI of differences 2.1, 3.8; P < 0.001), respectively. Additionally, the R : S ratio for AUC(0,24 h) and Ae(0,24 h) were significantly reduced in the itraconazole phase, while t(max), t(1/2) and renal clearance were constant during the study.
conclusionsThis study indicates that the stereoselective pharmacokinetics of fexofenadine are due to P-gp-mediated transport and its stereoselectivity is altered by itraconazole, a P-gp inhibitor. However, further study will be needed because the different affinities of the two enantiomers for P-gp have not been supported by in vitro studies.
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