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Pharmacokinetics of free and total flucloxacillin in newborn infants
Insights
Flucloxacillin pharmacokinetics in newborns show a longer half-life, influenced by gestational age. This antibiotic demonstrates reliable efficacy and safety for treating bacterial infections in neonates.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Infectious Diseases
Background:
- Bacterial infections pose significant risks to newborn infants.
- Understanding antibiotic pharmacokinetics in neonates is crucial for effective treatment.
- Flucloxacillin is a commonly used antibiotic, but its use in neonates requires specific pharmacokinetic data.
Purpose of the Study:
- To determine the pharmacokinetic profile of flucloxacillin in newborn infants.
- To compare neonatal flucloxacillin pharmacokinetics with adult data.
- To assess the safety and efficacy of flucloxacillin for treating bacterial infections in neonates.
Main Methods:
- Intravenous and oral administration of flucloxacillin to 9 newborn infants (gestational age 33-41 weeks).
- Analysis of plasma and urine concentrations using an open two-compartment model.
- Determination of plasma protein binding and distribution to blood cells and plasma water.
Main Results:
- The terminal half-life averaged 4 hours 38 minutes, significantly correlated with gestational age.
- Low plasma clearance (0.744 ml/min/kg) was observed, primarily due to small renal clearance.
- Mean apparent volume of distribution (Vz) was 0.280 L/kg, with considerable extravascular drug binding indicated.
- Oral bioavailability was 47.7%, comparable to adult values when adjusted for half-life.
- Plasma concentrations exceeded MIC values for Staphylococcus aureus, with minimal side effects observed.
Conclusions:
- Flucloxacillin exhibits distinct pharmacokinetic properties in newborns compared to adults, notably a longer half-life.
- Intravenous flucloxacillin is a reliable treatment for neonatal bacterial infections.
- Oral flucloxacillin may be considered in select cases, demonstrating adequate bioavailability and efficacy.
Abstract:
Flucloxacillin 50 mg/kg b.w. was administered intravenously (in combination with ampicillin/gentamicin) and orally (with amoxicillin) to 9 newborn infants (gestational age 33-41 weeks) to treat bacterial infections. The concentrations of flucloxacillin in plasma and urine after i.v. injection were analysed according to an open two-compartment model, and the plasma protein binding of flucloxacillin and its distribution to blood cells and plasma water in whole blood were determined. Considerable differences were found from values reported in adults. The terminal half-life averaged 4 h 38 min and was significantly correlated with gestational age. Plasma clearance was low (0.744 ml X min-1 X kg-1), due to the small renal clearance (0.182 ml X min-1 X kg-1), whilst non-renal clearance (0.563 ml X min-1 X kg-1) was approximately the same as in adults. The mean apparent volume of distribution of total drug (Vz) was 0.280 l/kg. The corresponding volume of distribution of unbound drug (Vu1 + Vu2) was 1.74 l/kg, which indicates considerable extravascular drug binding. The plasma protein binding of flucloxacillin (mean 86.3%) was significantly correlated with gestational age and the bilirubin/albumin concentration ratio. Bioavailability after oral administration, when corrected for changes in terminal half-life, was 47.7%, which is only slightly lower than that reported in adults. Since the plasma concentrations after both i.v. and oral administration were well above the MIC-values generally reported for Staphylococcus aureus, and since few side-effects were observed, intravenous injection or, in selected cases, orl administration of flucloxacillin appears to be a reliable therapy for the treatment of infections due to sensitive strains of S. aureus in premature newborn infants.