Aminoglycoside Dosage in Pediatric Patients: Considerations Regarding Pharmacokinetic-Based Dose Adjustment in Patients Requiring High versus Low Dose Therapy

Abstract

Pharmacokinetic-based adjustment of individual aminoglycoside dosage regimens is currently being utilized in the clinical setting in an attempt to avoid toxicity and/or enhance efficacy. In this report, comparisons have been made between initial and adjusted aminoglycoside dosage employed in toddlers and older children with cystic fibrosis or leukemia (high daily dose) and neonates (low daily dose) with suspected or proven infection. The initial versus adjusted mean aminoglycoside dosage was 14.1 and 17.0 mg/kg/day, respectively, in toddlers and older children with cystic fibrosis, and 7.1 and 11.5 mg/kg/day, respectively, in toddlers and older children with leukemia. Neonates with suspected or proven infection had an initial mean total daily dose of 7.4 mg/kg/day and the adjusted mean daily dose was 5.4 mg/kg/day. The use of a single pharmacokinetic dosing model for all patients, irrespective of evidence of increased or decreased drug elimination, results in widely differing drug dosages. Important and serious questions must be considered regarding the balance between efficacy and toxicity resulting from the rigid manner by which dosage adjustment protocols are employed.

Kinetics and Dose Calculations of Ampicillin and Gentamicin Given as Continuous Intravenous Infusion during Parenteral Nutrition in 88 Newborn Infants

“…It is a subject for discussion if gentamicin toxicity is related to peak values, trough values, the total dosage or to the area under the serum con centration time curve [18], In the present study, it was the aim to keep a steady state serum concentration of gentamicin of 4 pg/ml. No nephrotoxic reactions were seen in the patients.…”