Antimicrobial Original Research Paper Pharmacokinetics of once and twice daily dosing of intravenous tobramycin in paediatric patients with cystic fibrosis R. Brigg Turner 1 , Fawzy Elbarbry 1 , Lisa Biondo 2 1 Pacific University, School of Pharmacy, Hillsboro, OR, USA, 2 West Virginia University Healthcare, USA 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, Pv0.001), lower 24 hours AUC (92.8+28.7 vs 128.5+34.6, Pv0.001), and greater time less than the MIC (13.4 + 1.7 vs 3.9 + 3.1 hours, Pv0.001). Twice daily dosing failed to achieve goal C max :MIC for MICs w1.0 mg/l. Twice daily dosing may be a viable alternative to ODD in treating organisms with MICs j1.0 mg/l; however, with MICs w1.0 mg/l, ODD is likely necessary to achieve goal C max :MIC ratios. Keywords: Pharmacokinetics, Pharmacodynamics, Cystic fibrosis, Pulmonary exacerbation, Aminoglycoside Introduction In the Cystic Fibrosis Foundation (CFF) guidelines on treatment of pulmonary exacerbations, once daily dosing (ODD) of aminoglycosides is rec- ommended over thrice daily dosing. 1 The evidence in support of this recommendation is limited but suggests ODD and thrice daily dosing to be equally efficacious with data indicating decreased side effects with ODD. 1 Since the publication of these guidelines, national surveys conducted in both adult and paedia- tric centres have overwhelmingly shown ODD of tobramycin to be the most common method for dosing. National surveys have identified that the most frequently prescribed interval for adults (94%) and children (78%) is ODD, although a percentage of centres use twice daily dosing (TDD). 2,3 Traditionally, aminoglycosides have been adminis- tered by intermittent infusions thrice daily. Although adoption of ODD of aminoglycosides in the cystic fibrosis (CF) population lagged behind the general population, several advantages to this modality led to its widespread use. Aminoglycoside ODD is designed to enhance bactericidal activity by produ- cing a high peak concentration (C max ) to minimum inhibitory concentration (MIC) ratio while benefit- ting from the post-antibiotic effect (PAE). 4,5 A C max : MIC ratio of 8–10 is considered optimal and corre- lates with better clinical outcomes in patients with CF. 6 In addition to C max , area under the concen- tration-time curve from 0 to 24 hours (AUC) has been associated with efficacy with an AUC:MIC ratio w80 predicting positive outcomes. 6 In contrast, increased time that drug concentration is below the MIC (T v MIC) has been associated with bacterial regrowth at the end of the dosing interval and the development of resistance in two small studies of CF patients. 7,8 Once daily dosing has previously been shown to produce high C max :MIC ratios but high T v MIC. 5 Twice daily dosing may produce adequate C max :MIC and AUC:MIC ratios necessary for efficacy while limiting T v MIC and may be useful for prevention of resistance development. Despite consistent use, no studies have reported the pharmacokinetics of TDD of tobramycin in paedia- tric patients with CF. The purpose of this study is to describe the pharmacokinetics and pharmacody- namics of TDD in comparison to ODD for the treat- ment of acute pulmonary exacerbations in children with CF. Materials and Methods This single centre, retrospective study was approved by the West Virginia University (Morgantown, WV) institutional review board. In 2009, our hospital developed a protocol to guide dosing of tobramycin in paediatric CF patients, which recommends Correspondence to: R. Brigg Turner, Pacific University, School of Pharmacy, 6 222 SE 8th Ave Suite 451, 7 Hillsboro, OR 97123, USA. Email: brigg.turner@pacificu.edu ß 2015 Edizioni Scientifiche per l’Informazione su Farmaci e Terapia DOI 10.1179/1973947815Y.0000000077 Journal of Chemotherapy 2015 VOL. 00 NO.0 1