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Pharmacodynamics of Voriconazole in Children
- Source :
- Antimicrobial Agents and Chemotherapy, 60(4), 2336-2342. AMER SOC MICROBIOLOGY
- Publication Year :
- 2016
-
Abstract
- Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC 50 ) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC 50 )/15.4 predicted terminal galactomannan ( P = 0.003), and a ratio of >6 suggested a lower terminal galactomannan level ( P = 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival.
- Subjects :
- 0301 basic medicine
Oncology
Male
INVASIVE ASPERGILLOSIS
Antifungal Agents
Pharmacology
Aspergillosis
GUIDELINES
030226 pharmacology & pharmacy
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Mannans
chemistry.chemical_compound
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings]
0302 clinical medicine
Information Science::Information Science::Computing Methodologies::Software [Medical Subject Headings]
GALACTOMANNAN
Pharmacology (medical)
Precision Medicine
Child
skin and connective tissue diseases
education.field_of_study
Área bajo la curva
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability [Medical Subject Headings]
3. Good health
Infectious Diseases
INFECTIONS
Area Under Curve
Child, Preschool
DISEASES
SAFETY
Female
Drug Monitoring
Antifúngicos
medicine.drug
Antifungal
medicine.medical_specialty
Dose
medicine.drug_class
030106 microbiology
Population
SOCIETY
Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Triazoles::Voriconazole [Medical Subject Headings]
Microbial Sensitivity Tests
03 medical and health sciences
Galactomannan
Chemicals and Drugs::Carbohydrates::Polysaccharides::Mannans [Medical Subject Headings]
Pharmacokinetics
Diseases::Bacterial Infections and Mycoses::Infection::Skin Diseases, Infectious::Dermatomycoses::Hyalohyphomycosis::Aspergillosis [Medical Subject Headings]
Internal medicine
medicine
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Bayes Theorem [Medical Subject Headings]
Humans
Computer Simulation
education
KINETICS
Voriconazole
Models, Statistical
business.industry
Aspergillus fumigatus
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Area Under Curve [Medical Subject Headings]
ANTIFUNGAL THERAPY
Galactose
Fungal Polysaccharides
medicine.disease
EFFICACY
Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antifungal Agents [Medical Subject Headings]
Mananos
chemistry
Aspergilosis
Pharmacodynamics
business
Probabilidad
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 10986596
- Volume :
- 60
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....4c8c67bf7597abb4cea39527f245a814