Efficacy and toxicity of once versus twice daily regimens of amikacin in febrile neutropenic pediatric cancer patients

Abstract

PurposeTo compare the pharmacokinetic profile, clinical efficacy and toxicity of once-daily dosing of amikacin compared to twice-daily dosing among pediatric cancer patients with fever and neutropenia. Methods134 pediatric patients with hematological malignancies were randomly assigned to receive 15mg/kg/day amikacin intravenously, either once or twice-daily dosing. For pharmacokinetics, two blood samples were obtained from each patient, the first sample was taken after 1h from the beginning of infusion and the second sample was taken after 3h from the first sample. Treatment success was considered when the patient improved without a change in the assigned antibiotic regimen or mortality from infection. Nephrotoxicity was assessed by following the increase in serum creatinine level. ResultsPharmacokinetic data revealed superiority in once-daily dosing where maximum concentration Cmax, area under the concentration time curve in 24h AUC24 and elimination half-life t1/2 were a significantly higher while minimum concentration Cmin, elimination rate constant Ke and clearance CL were significantly lower in once-daily dosing compared to the twice-daily dosing. Clinical response achieved in 76.8% in once-daily group compared to 69.2% in twice-daily group. Nephrotoxicity was recorded in two patients in once-daily group and six patients in the twice-daily group. After stratifying our patients according to age, a significant increase was observed in the volume of distribution V and CL in pediatrics with age ⩽five compared to >five years. Cmax and AUC24 were significantly lower in the age group of ⩽five years. ConclusionsClinical efficacy and nephrotoxicity were slightly improved in once-daily dosing compared to twice-daily dosing.