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A Population and Developmental Pharmacokinetic Analysis To Evaluate and Optimize Cefotaxime Dosing Regimen in Neonates and Young Infants
- Source :
- Antimicrobial Agents and Chemotherapy, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2016, 60 (11), pp.6626-6634. ⟨10.1128/AAC.01045-16⟩, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2016, 60 (11), pp.6626-6634. 〈10.1128/AAC.01045-16〉
- Publication Year :
- 2016
- Publisher :
- American Society for Microbiology, 2016.
-
Abstract
- Cefotaxime is one of the most frequently prescribed antibiotics for the treatment of Gram-negative bacterial sepsis in neonates. However, the dosing regimens routinely used in clinical practice vary considerably. The objective of the present study was to conduct a population pharmacokinetic study of cefotaxime in neonates and young infants in order to evaluate and optimize the dosing regimen. An opportunistic sampling strategy combined with population pharmacokinetic analysis using NONMEM software was performed. Cefotaxime concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Developmental pharmacokinetics-pharmacodynamics, the microbiological pathogens, and safety aspects were taken into account to optimize the dose. The pharmacokinetic data from 100 neonates (gestational age [GA] range, 23 to 42 weeks) were modeled with an allometric two-compartment model with first-order elimination. The median values for clearance and the volume of distribution at steady state were 0.12 liter/h/kg of body weight and 0.64 liter/kg, respectively. The covariate analysis showed that current weight, GA, and postnatal age (PNA) had significant impacts on cefotaxime pharmacokinetics. Monte Carlo simulations demonstrated that the current dose recommendations underdosed older newborns. A model-based dosing regimen of 50 mg/kg twice a day to four times a day, according to GA and PNA, was established. The associated risk of overdose for the proposed dosing regimen was 0.01%. We determined the population pharmacokinetics of cefotaxime and established a model-based dosing regimen to optimize treatment for neonates and young infants.
- Subjects :
- 0301 basic medicine
Male
Pediatrics
Cefotaxime
[ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics
030226 pharmacology & pharmacy
0302 clinical medicine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Tandem Mass Spectrometry
Pharmacology (medical)
Drug Dosage Calculations
Chromatography, High Pressure Liquid
Volume of distribution
education.field_of_study
Gestational age
3. Good health
Anti-Bacterial Agents
[ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Intensive Care Units
Infectious Diseases
Female
Monte Carlo Method
medicine.drug
medicine.medical_specialty
030106 microbiology
Population
Gestational Age
Drug Administration Schedule
03 medical and health sciences
Pharmacokinetics
Sepsis
Périnatalité
medicine
Humans
Computer Simulation
Dosing
education
Pharmacology
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
Models, Statistical
business.industry
Body Weight
Infant, Newborn
[ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Infant
NONMEM
Pharmacodynamics
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
business
Gram-Negative Bacterial Infections
Subjects
Details
- Language :
- English
- ISSN :
- 00664804 and 10986596
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2016, 60 (11), pp.6626-6634. ⟨10.1128/AAC.01045-16⟩, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2016, 60 (11), pp.6626-6634. 〈10.1128/AAC.01045-16〉
- Accession number :
- edsair.doi.dedup.....24c97df1785cb5794ea6e38204e672d1