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[Pharmacokinetics in neonates and infants following administration of amikacin]
Insights
This study investigated amikacin sulfate pharmacokinetics in neonates and infants, finding that drug levels and urinary excretion increase with age. Pharmacokinetic models were applied to determine optimal dosing strategies for these young populations.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pediatric Pharmacology
- Aminoglycoside Antibiotics
Context:
- Amikacin sulfate is crucial for treating bacterial infections in neonates and infants.
- Understanding drug disposition in these vulnerable populations is essential for safe and effective therapy.
- Previous pharmacokinetic data in pediatric populations, especially neonates, is limited.
Purpose:
- To evaluate the pharmacokinetics of amikacin sulfate following intramuscular and intravenous administration in neonates and infants.
- To analyze blood and urinary drug levels in relation to age and dosage.
- To determine appropriate pharmacokinetic models for dose optimization in pediatric patients.
Summary:
- Amikacin sulfate administered via intramuscular or intravenous routes showed age-dependent blood and urinary levels in neonates (8-28 days) and infants (35 days-1 year).
- Urinary recovery rates and drug clearance increased with age, suggesting improved renal function.
- One-compartment and two-compartment pharmacokinetic models were applicable, with parameters like Vd and Kel showing age-related correlations, guiding dosing adjustments.
Impact:
- Provides crucial pharmacokinetic data for amikacin sulfate in neonates and infants, aiding in the development of evidence-based dosing guidelines.
- Facilitates optimized therapeutic drug monitoring and improved treatment outcomes for pediatric patients.
- Highlights the importance of age-specific pharmacokinetic considerations for aminoglycoside therapy in early life.
Abstract:
Sixteen neonates (at ages of 8 to 28 days) and 8 infants (at ages of 35 days to 1 year), who were in need of treatment with amikacin sulfate, were subjected to the present study. The drug was administered by intramuscular route (1.39 to 3.13 mg/kg) or by intravenous drip infusion over a 30 to 60 minutes period (2.94 to 6.00 mg/kg). Blood levels and urinary excretion of the drug were investigated with these subjects. The blood levels were also analyzed according to pharmacokinetic models. 1. When the drug was administered intramuscularly to neonates at average doses of 1.49 and 2.96 mg/kg and to infants at average doses of 2.97 mg/kg peak levels of 2.74, 6.53 and 8.55 micrograms/ml, respectively, were attained at 30 minutes after dosing. 2. When the drug was administered to neonates at average doses of 3.01 and 5.89 mg/kg by intravenous drip infusion over a 30 to 60 minutes period and to infants at average doses of 2.97 and 6.00 mg/kg in the same manner, peak levels of 7.70, 20.9, 9.40 and 23.0 micrograms/ml, respectively, were attained at the end of the intravenous drip infusion. 3. Urinary levels and recovery rates tended to increase with ages of these subjects. Urinary recovery rates for the neonates and the infants were 41.0 and 58.9%, respectively, on the average. 4. From a pharmacokinetic analysis of blood levels of the drug, it was concluded that, in any of the subjects who received the drug intramuscularly or by intravenous drip infusion, it would be possible to use the one-compartment open model. In the subjects who received the drug by intravenous drip infusion, however, it was determined the two-compartment open model would be the choice. 5. In the neonates and the infants, whose blood levels were analyzed according to the one-compartment open model, Ka values averaged 7.51 and 6.62 hr-1, respectively, with respective average Kel values of 0.32 and 0.66 hr-1. Average Vd values obtained were 0.36 and 0.26 L/kg, respectively. There was a negative correlation between the Vd values and the ages of the subjects, while there was a positive correlation between the Kel values and the ages. 6. Appropriate conditions for administering the drug by intravenous drip infusion to neonates and infants at ages of more than 1 week were investigated taking observed blood levels and achieved peak levels and trough levels calculated using the one-compartment open model into account.(ABSTRACT TRUNCATED AT 400 WORDS)