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

Autor: Thierry Buclin, Laurent A. Decosterd, Karin Fattinger, C. Csajka, Jérôme Biollaz, Jean-Luc Pagani, Jacques Bille
Rok vydání: 2002
Předmět:
Adult
Male
medicine.medical_specialty
Antifungal Agents
Population
Gastroenterology
Models
Biological
Oropharyngeal Candidiasis
Pharmacokinetics
Candidiasis
Oral
Drug Resistance
Fungal
Internal medicine
medicine
Humans
Pharmacology (medical)
education
Fluconazole
Mycosis
Randomized Controlled Trials as Topic
Pharmacology
Volume of distribution
education.field_of_study
medicine.diagnostic_test
AIDS-Related Opportunistic Infections
business.industry
AIDS-Related Opportunistic Infections/prevention & control
Antifungal Agents/pharmacokinetics
Antifungal Agents/therapeutic use
Candidiasis
Oral/prevention & control
Female
Fluconazole/pharmacokinetics
Fluconazole/therapeutic use
Middle Aged
Treatment Outcome
General Medicine
medicine.disease
Tolerability
Therapeutic drug monitoring
Immunology
business
medicine.drug
Zdroj: Europe PubMed Central
European journal of clinical pharmacology, vol. 57, no. 10, pp. 723-727
ISSN: 0031-6970
Popis: Objectives: 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 (150mg weekly) versus placebo in human immunodeficiency virus-positive (HIV+) patients with oropharyngeal candidiasis. Methods: Population pharmacokinetic parameters of fluconazole determined from 458 serum drug concentration measurements obtained over 37months 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. Results: Fluconazole kinetics were best described by a one-compartment model with first-order oral absorption 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 0.79l/h, the volume of distribution 57l and the absorption constant (ka) 0.93h-1. Inter-occasion variability in clearance (45%) was large relative to inter-subject 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. Conclusion: 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
Databáze: OpenAIRE
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