Amikacin pharmacokinetics in pediatric patients with malignancy

Abstract

The pharmacokinetics of anmikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and nonnal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 mim produced concentrations in serum of 29.3 ± 5.7 jig/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 ± 1.7 jsg/ml and at 6 h of 1.2 ± 0.3 ,ug/ml. The serum half-life was 1.24 ± 0.09 h, volume of distribution was 0.26 ± 0.02 liter/kg, and total body clearance rate was 131 ± 10 ml/min per 1.73 m2. No accumulation of amnikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.

Development and application of neonatal physiology‐based pharmacokinetic models of amikacin and fosfomycin to assess pharmacodynamic target attainment

“…As the performance of the adult amikacin PBPK model was within acceptable limits, we scaled the model without structural modification, to create a pediatric PBPK model. Simulations with this model visually matched the test data set well (Figure 2b) and validated against the available pediatric amikacin PK datasets 35,[37][38][39] (Table S6) with weighted geometric mean AUC and C max ratios of 1.13 and 1.08, respectively.…”

“…(b) Pediatric amikacin PBPK model simulating a 5 mg/kg i.v. infusion over 60 min in children aged 1–16 years, with overlaid population mean observed data from Cleary et al 35 . (c) Neonatal fosfomycin PBPK model simulating a 3 mg/kg i.v.…”

Effect of Peritoneal Dialysis on Serum Concentrations of Three Drugs Commonly Used in Pediatric Patients

“…In patients with renal failure while receiving peritoneal dialysis, the major route of amikacin elimination is via the dialysate. In our patient, approximately 30 mg (mean of 1.22 mg/cycle) of amikacin was removed by 27 cycles of dialysis over 57 h. This amount accounts for a serum concen tration decrease of 16.0 pg/ml according to an estimated volume of distri bution of 0.25 1/kg [27,28]. The serum amikacin concentration of our patient was 34.0 pg/ml at the beginning of the dialysis treatment and it declined to 17.0 pg/ml after 27 cycles of peritoneal dialysis.…”

Multiple‐dose amikacin kinetics in pediatric oncology patients

“…Fifty patients ranging in age from 1 to 17 yr admitted to the pediatric service of the University of Texas System Cancer Center-M. D. Anderson Hospital and Tumor Institute comprised the total population and are described elsewhere. 6 While all patients were studied for one dosing interval, 8 had serum amikacin concentration-time profiles determined for more than one dosing interval. The results in this subgroup form the basis of this report.…”