Amoxicillin pharmacokinetics in (preterm) infants aged 10 to 52 days: effect of postnatal age

Area of Science:

• Pharmacology
• Neonatal Medicine
• Clinical Pharmacy

Background:

• Amoxicillin is frequently prescribed for neonatal infections.
• Optimizing amoxicillin dosing in neonates is crucial for efficacy and safety.
• Limited pharmacokinetic data exists for amoxicillin in older neonates.

Purpose of the Study:

• To determine amoxicillin pharmacokinetic parameters in newborn infants aged 10 to 52 days.
• To establish an improved amoxicillin dosing regimen for this population.
• To achieve target plasma amoxicillin concentrations and time above minimum inhibitory concentration.

Main Methods:

• Amoxicillin plasma concentrations were measured using reversed-phase high-performance liquid chromatography.
• Pharmacokinetic parameters including elimination constant, volume of distribution, clearance, and half-life were calculated.
• Simulation studies were conducted using observed pharmacokinetic data.

Main Results:

• Amoxicillin elimination constant (K(el)) was 0.27 +/- 0.10 h(-1).
• Volume of distribution corrected for body weight (V/W) was 0.66 +/- 0.27 L/kg.
• Total body clearance corrected for body weight (CL/W) was 0.18 +/- 0.10 Lkg(-1)h(-1), and elimination half-life (t(1/2)) was 3.0 +/- 1.3 hours.
• Body clearance was twofold greater than in younger neonates.

Conclusions:

• The study provides key pharmacokinetic data for amoxicillin in older neonates.
• A proposed amoxicillin dose of 40 mg/kg every 8 hours may be effective for infants >9 days old.
• Prospective evaluation of the new dosage regimen is recommended before clinical implementation.