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Amoxicillin pharmacokinetics in preterm infants with gestational ages of less than 32 weeks
J J Huisman-de Boer1, J N van den Anker, M Vogel
1Department of Pediatrics, Erasmus University, Rotterdam, The Netherlands.
Insights
This study found that a 25 mg/kg intravenous dose of amoxicillin every 12 hours in preterm infants (gestational age < 32 weeks) achieves therapeutic serum levels. These amoxicillin levels are sufficient to combat common neonatal infections.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Background:
- Amoxicillin is a common antibiotic for neonatal infections.
- Pharmacokinetic data in preterm infants is crucial for optimizing dosing.
- Understanding amoxicillin's behavior in neonates informs treatment strategies.
Purpose of the Study:
- To evaluate the pharmacokinetics of amoxicillin in preterm infants.
- To determine if a specific amoxicillin dosage regimen achieves therapeutic concentrations.
- To correlate amoxicillin clearance with renal function in neonates.
Main Methods:
- Multiple-dose intravenous amoxicillin (25 mg/kg every 12 hours) was administered to 17 preterm infants.
- Serum amoxicillin concentrations were measured using high-performance liquid chromatography.
- Glomerular filtration rate was assessed via 24-hour inulin infusion.
Main Results:
- Amoxicillin followed a one-compartment open model with a half-life of 6.7 hours.
- Mean peak and trough serum amoxicillin levels were 53.6 and 16.0 mg/L, respectively.
- Amoxicillin clearance and volume of distribution increased with gestational age and were similar to inulin clearance.
Conclusions:
- A 25 mg/kg every 12-hour intravenous amoxicillin dose is effective in preterm infants (< 32 weeks gestation).
- Achieved serum amoxicillin levels exceed the minimum inhibitory concentration for common neonatal pathogens.
- Amoxicillin dosing in neonates should consider gestational age and renal function.
Abstract:
The multiple-dose pharmacokinetics of amoxicillin (AM [administered twice daily in a 25-mg/kg of body weight intravenous dose]) in 17 preterm infants (11 males; gestational age, 29 +/- 1.9 weeks; birth weight, 1,175 +/- 278 g) were evaluated on day 3 of life. Blood samples were collected from an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after the intravenous dose. A high-performance liquid chromatography method was used to determine AM concentrations in serum. AM pharmacokinetics followed a one-compartment open model. The glomerular filtration rates of all patients were simultaneously studied by means of the 24-h continuous inulin infusion technique. The elimination half-life, apparent volume of distribution, and total body clearance of AM (mean +/- standard deviation) were 6.7 +/- 1.7 h, 584 +/- 173 ml, and 62.4 +/- 23.3 ml/h, respectively. The mean (+/- standard deviation) AM peak and trough levels were 53.6 +/- 9.1 and 16.0 +/- 4.9 mg/liter, respectively. All infants had a serum trough level above 5 mg/liter. The total body clearance and apparent volume of distribution of AM and the clearance of inulin increased significantly with increasing gestational age. The total body clearance of AM (1.0 +/- 0.4 ml/min) and the clearance of inulin (1.0 +/- 0.3 ml/min) were similar. The total body clearance of AM increased significantly with increasing clearance of inulin. We conclude that an AM dose of 25 mg/kg every 12 h given to preterm infants in the first week of life with gestational ages of less than 32 weeks results in serum levels well above the MIC for major microorganisms involved in neonatal infections.