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[Posology of amikacin in newborn infants, adapted to the postconceptional age]
1Service de Néonatologie, Hôpital Laënnec, Centre Hospitalier Universitaire de Nantes.
Insights
Optimizing amikacin dosing for neonates based on postconceptional age (PCA) improves therapeutic drug monitoring. This PCA-adapted dosage strategy enhances maximal amikacin concentrations while maintaining safe trough levels.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Clinical Pharmacy
Context:
- Amikacin is a critical antibiotic for neonatal infections.
- Accurate dosing is essential due to immature organ function in neonates.
- Previous dosing regimens may not optimize therapeutic outcomes.
Purpose:
- To establish and validate an amikacin dosing regimen tailored to neonatal postconceptional age (PCA).
- To correlate amikacin pharmacokinetic parameters with PCA.
- To improve amikacin therapeutic drug monitoring in neonates.
Summary:
- Two studies involving 63 and 64 neonates (26-45 weeks PCA) evaluated amikacin plasma levels.
- Initial study established a PCA-related dosage, finding half-life strongly correlated with PCA.
- A refined dosage of 10 mg/kg based on PCA was validated, yielding higher peak concentrations and fewer sub-therapeutic trough levels.
Impact:
- The PCA-adapted amikacin dosage significantly improves pharmacokinetic profiles in neonates.
- This strategy enhances the likelihood of achieving therapeutic amikacin concentrations.
- Optimized dosing can lead to improved treatment efficacy and reduced risk of toxicity in neonates.
Abstract:
Two consecutive studies of amikacin plasma levels were performed in 63 and 64 neonates whose postconceptional age (PCA) ranged from 26 to 45 weeks. The first study, using a dose of 7.5 mg/kg every 12 hours, permitted to establish a dosage related to PCA. Half-life elimination of amikacin was strongly correlated with PCA (r = -0.42, p = 0.0009). The apparent volume of distribution was correlated with none of the variables studied. The mean volume of distribution was 640 +/- 190 ml/kg. From these data, the inferred dosage was 10 mg/kg, given at intervals of time predetermined as a function of PCA. A second prospective study proved the value of this PCA adapted dosage. The maximal concentrations obtained were higher (21.6 +/- 5.9 vs 18.5 +/- 4.6 micrograms/ml, p less than 0.001), the nadir concentrations were not significantly increased (5.7 +/- 3.1 vs 5.2 +/- 3.7 micrograms/ml, NS) and the number of nadir concentrations outside the desired interval of 2-8 micrograms/ml was smaller (p less than 0.01).