Once- versus Twice-Daily Administration of Amikacin in Pediatric Patients with Bronchopneumonia: Plasma Drug Concentration and Bayesian Pharmacokinetics Estimation

Abstract

TO THE EDITOR: Once-daily use of aminoglycosides has been shown to be safe and effective in adults; however, there has been limited experience in children. 1 Also, the Bayesian pharmacokinetic approach for individualizing dosage of aminoglycosides is poorly documented in pediatric patients. 2 We determined the amikacin plasma concentrations achieved and the pharmacokinetics (estimated by the Bayesian approach) in pediatric patients with bronchopneumonia with once-or twice-daily dosing.Methods. Twenty-one patients (mean ± SD age 1.45 ± 1.34; mean ± SD body weight 8.4 ± 4.0 kg) diagnosed with bronchopneumonia were empirically treated with ampicillin 100 mg/kg/d and amikacin given either once daily (n = 10; 15 mg/kg/d) or twice daily (n = 11; 7.5 mg/kg q12h). Intravenous amikacin was infused over 30 minutes and all patients had good renal function (serum creatinine ≤1 mg/dL). Exclusion criteria included serum creatinine >1.4 mg/dL, granulocytopenia, proven otitis media or hearing loss, or history of aminoglycoside administration, including amikacin, within at least seven days of entry into the study. Two amikacin plasma concentrations were determined in every patient using TDxFLx (a peak value 30 minutes after the end of infusion and a trough value just before the next infusion). The clearance (Cl) and apparent volume of distribution (V d ) for amikacin were calculated based on characteristics (e.g., age, weight) of individual patients and measured plasma concentrations of the drug. A pharmacokinetics software package (Abbott Diagnostica, Wiesbaden, Germany) was used to analyze serum concentration data. The mean prediction error (me) for estimation of bias and root mean 2 error (rm 2 ) for estimation of precision, in addition to their corresponding CIs as defined by Sheiner and Beal, 3 were used to evaluate predictive performance of these methods.