Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Δευτέρα 3 Δεκεμβρίου 2018

Population Pharmacokinetics and Dosing Optimization of Amoxicillin in Neonates and Young Infants [Pharmacology]

Backgrounds: Amoxicillin is widely used to treat bacterial infections in neonates. However, considerable inter-center variability in dosage regimens of antibiotic exist in clinical practice. Pharmacokinetics of amoxicillin has been described in only a few preterm neonates. Thus, we aimed to evaluate population pharmacokinetics of amoxicillin through a large samples covered entire age range of neonates and young infants, and establish evidence-based dosage regimens based on developmental pharmacokinetics–pharmacodynamics.

Methods: This is a prospective, multi-center, pharmacokinetic study using an opportunistic sampling design. Amoxicillin plasma concentrations were determined using high performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM.

Results: A total of 224 pharmacokinetic samples from 187 newborns (postmenstrual age range: 28.4 – 46.3 weeks) were available for analysis. A 2-compartment model with first-order elimination was used to describe population pharmacokinetics. Covariate analysis showed that current weight, postnatal age and gestational age were significant covariates. The final model was further validated for predictive performance in an independent cohort of patients. Monte Carlo simulation demonstrated that for early-onset sepsis, the currently used dosage regimen (25mg/kg BID) resulted in 99.0% of premature neonates and 87.3% of term neonates achieving the pharmacodynamic target (% time above MIC), using MIC breakpoint of 1 mg/L. For late-onset sepsis, 86.1% of premature neonates treated with 25mg/kg TID and 79.0% of term neonates receiving 25mg/kg QID reached the pharmacodynamic target, using MIC breakpoint of 2 mg/L.

Conclusion: The population pharmacokinetics of amoxicillin was assessed in neonates and young infants. A dosage regimen was established based on developmental pharmacokinetics-pharmacodynamics.



https://ift.tt/2RxTwYS

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.