Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients.

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Serval ID
serval:BIB_0E4686924252
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients.
Journal
European journal of clinical pharmacology
Author(s)
Csajka C., Décosterd L.A., Buclin T., Pagani J.L., Fattinger K., Bille J., Biollaz J.
ISSN
0031-6970 (Print)
ISSN-L
0031-6970
Publication state
Published
Issued date
12/2001
Peer-reviewed
Oui
Volume
57
Number
10
Pages
723-727
Language
english
Notes
Publication types: Clinical Trial ; Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
To determine fluconazole population pharmacokinetics and explore the relationships between fluconazole average concentration and treatment effectiveness or microbiological resistance induction during a study aimed at evaluating the efficacy, tolerability and resistance induction after secondary prevention with fluconazole (150 mg weekly) versus placebo in human immunodeficiency virus-positive (HIV+) patients with oropharyngeal candidiasis.
Population pharmacokinetic parameters of fluconazole determined from 458 serum drug concentration measurements obtained over 37 months in 132 HIV + patients not receiving highly active antiretroviral therapy. Mean estimates and variabilities were generated using non-linear regression analysis. Logistic and linear regression analyses were used to explore the relationships between the estimated average concentration of fluconazole and candidiasis relapse or fungal resistance towards fluconazole.
Fluconazole kinetics were best described by a one-compartment model with first-order oral absorp tion from the gastrointestinal tract. The pharmacokinetics were influenced only by body weight. No effect was observed for gender, age, height or lymphocyte CD4 counts. The mean apparent population clearance was 0.79 l/h, the volume of distribution 571 and the absorption constant (ka) 0.93 h(-1). Inter-occasion variability in clearance (45%) was large relative to intersubject variability (21%). Taking into account the average fluconazole concentration or the time above the minimal inhibitory concentrations did not clinically improve the prediction of the occurrence of oropharyngeal relapse or microbiological resistance.
The relationship between fluconazole concentrations and preventive effectiveness was poor. Together with the rather large inter-occasion variability in fluconazole clearance, this suggests no role of therapeutic drug monitoring in optimising fluconazole treatment for secondary prevention.

Keywords
AIDS-Related Opportunistic Infections/prevention & control, Adult, Antifungal Agents/pharmacokinetics, Antifungal Agents/therapeutic use, Candidiasis, Oral/prevention & control, Drug Resistance, Fungal, Female, Fluconazole/pharmacokinetics, Fluconazole/therapeutic use, Humans, Male, Middle Aged, Models, Biological, Randomized Controlled Trials as Topic, Treatment Outcome
Pubmed
Open Access
Yes
Create date
25/01/2008 10:48
Last modification date
01/10/2019 6:16
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