Extended Interval Tobramycin Pharmacokinetics in a Pediatric Patient With Primary Ciliary Dyskinesia Presenting With an Acute Respiratory Exacerbation

Abstract

The pharmacokinetics of tobramycin in patients with ciliary dyskinesia have not been previously reported. A 10-year-old female patient with primary ciliary dyskinesia was admitted to the general pediatrics floor with an acute respiratory exacerbation after several months of worsening lung function that was unresponsive to oral antibiotics. Extrapolating from cystic fibrosis dosing regimens, she was given intravenous tobramycin 320 mg (10.3 mg/kg/day) on admission as a result of concern for a Pseudomonas aeruginosa infection. Two-point pharmacokinetic monitoring revealed a maximum serum concentration (Cmax) of 18.9 mg/L and a 24-hour area under the curve (AUC_0-24hr) of 58.8 (mg × hr)/L, as well as a volume of distribution (Vd) of 0.5 L/kg and an elimination rate (Ke) of 0.34 hr^-1. After a dosage increase to tobramycin 400 mg (12.8 mg/kg/day), pharmacokinetic parameters on 2 assessments were as follows: Vd 0.37 to 0.39 L/kg, Ke 0.33 to 0.39 hr^-1, Cmax 27.8 to 28.7 mg/L, and AUC_0-24h 78.4 to 89.4 (mg × hr)/L. This was the first case report of aminoglycoside pharmacokinetics in a patient with ciliary dyskinesia. The administration of larger doses (up to 12.8 mg/kg/day) of extended-interval tobramycin, similar to the treatment recommendation of at least 10 mg/kg/day for cystic fibrosis patients, was necessary in this patient to achieve serum concentrations that were appropriate for treatment.

Keywords: aminoglycoside; extended-interval; mucociliary clearance; primary ciliary dyskinesia; tobramycin.