Pharmacokinetics of once-daily amikacin in pediatric patients

OBJECTIVE: To study the pharmacokinetic parameters of a once-daily regimen of amikacin (15 mg/kg) in association with other antimicrobial agents in 35 children with severe Gram-negative infections. METHODS: A Bayesian approach was developed to optimize the amikacin regimen. The predictive performance was assessed by computing bias and precision. Each patient was evaluated for toxicity after 5 days of treatment. RESULTS: Peak amikacin concentrations on days 2 and 5 of therapy averaged 31.3 plus minus 9.0 mg/L and 32.4 plus minus 7.4 mg/L, respectively. To achieve peak serum concentrations between 30 and 40 mg/L, individualized dosage was necessary in 19 of 35 children. The pharmacokinetic parameters showed large interindividual variations, with a mean half-life of 2 h and a mean volume of distribution of 0.36 L/kg. No nephrotoxicity was observed in any of the children. After individualization of dosage on the basis of one measurement of peak concentration, no significant differences were observed between predicted and subsequently measured amikacin concentrations. CONCLUSIONS: Once-daily dosage of amikacin (15 mg/kg) is well tolerated in pediatric patients; however, a loading dose of 20 mg/kg is recommended to achieve a therapeutic peak value between 30 and 40 mg/L. Initial serum monitoring is essential in a population such as children, with wide interpatient variability. Using the Bayesian approach, the amikacin regimen in children can then be predicted with minimal bias and good precision.