Pharmacokinetics of once-daily amikacin in pediatric patients

Abstract

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.

DNA and RNA damage by Cu(II)‐amikacin complex

“…Ami hydroperoxides, formation of which was suggested by MS experiments, may also be involved in these reactions. Concentrations of amikacin used in all experiments were comparable to its therapeutic ones, which are in the range of 50–70 µ m in blood serum [45–48]. The issue of intracellular copper bioavailability is currently debated [49–51].…”

Pharmacokinetics of a high dose of amikacin administered at extended intervals to neonatal foals

“…The magnitude of early plasma aminoglycoside concentrations and the ratio of peak plasma concentration to the MIC of the offending microbe are directly correlated with clinical outcome in human patients. 12,[17][18][19][20][21] The disposition of high-dose, once-daily administration of gentamicin has been described in adult hors-Objective-To determine disposition kinetics of amikacin in neonatal foals administered high doses at extended intervals. 10 Postantibiotic enhancement of phagocytosis of aminoglycoside-exposed bacteria by host leukocytes may be an additional benefit of high-dose aminoglycoside pharmacologic characteristics, as evidenced by an increase in postantibiotic enhancement of human leukocytes against E coli and Staphylococcus aureus.…”

Antibiotics and its altered pharmacokinetics in the pediatric population : An evidence-based review

“…A once-daily dosage of amikacin (15 mg/kg per day), with a loading dose of 20mg/kg/day, is preferred over frequent administration and is well tolerated in pediatric patients (1-12 years) due its relative ef icacy and reduced potency for renal toxicity (Alqahtani et al, 2018;Belfayol et al, 1996). The volume of distribution of amikacin is greater in children than in adults and it is inversely related with age.…”

“…The volume of distribution of amikacin is greater in children than in adults and it is inversely related with age. This interindividual variability in volume of distribution has a direct effect on the targeted therapeutic peak levels and clearance of amikacin (Belfayol et al, 1996). Therefore, an individualized dosage regimen, along with therapeutic drug monitoring, is proposed for amikacin due to its narrow therapeutic index and wide variability in pediatric patients.…”