Pharmacokinetics of once and twice daily dosing of intravenous tobramycin in paediatric patients with cystic fibrosis

Abstract

The optimal dosing of intravenous tobramycin for treatment of pulmonary exacerbations in paediatric cystic fibrosis (CF) patients has not been completely delineated. We performed a retrospective study evaluating the pharmacokinetics and pharmacodynamics of once daily dosing (ODD) of IV tobramycin compared to twice daily dosing (TDD). Fifty-nine and 44 patients were included in the ODD and TDD groups, respectively. Once daily dosing achieved higher C _max as compared to TDD (29.5 ± 11.0 vs 19.0 ± 4.9, P < 0.001), lower 24 hour AUC (92.8 ± 28.7 vs 128.5 ± 34.6, P < 0.001), and greater time that drug concentration was below the minimum inhibitory concentration (MIC) (13.4 ± 1.7 vs 3.9 ± 3.1 hour, P < 0.001). Twice daily dosing failed to achieve goal C _max:MIC for MICs >1.0 mg/l. Twice daily dosing may be a viable alternative to ODD in treating organisms with MICs ≤ 1.0 mg/l; however, with MICs >1.0 mg/l, ODD is likely necessary to achieve goal C _max:MIC ratios.

Keywords:

• Pharmacokinetics
• Pharmacodynamics
• Cystic fibrosis
• Pulmonary exacerbation
• Aminoglycoside