title: 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 Cmax 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 Cmax: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 Cmax:MIC ratios.
authors.affiliation: a School of Pharmacy , Pacific University , Hillsboro , OR USA.
authors.forename: R
authors.initials: R
authors.lastname: Brigg Turner
authors.affiliation: a School of Pharmacy , Pacific University , Hillsboro , OR USA.
authors.forename: Fawzy
authors.initials: F
authors.lastname: Elbarbry
authors.affiliation: b West Virginia University Medicine , Morgantown , WV , USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Biondo
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000150:complications / Q000188:drug therapy; D008297:Male; D012189:Retrospective Studies; D014031:Tobramycin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014031:Tobramycin
keywords: Aminoglycoside; Cystic fibrosis; Pharmacodynamics; Pharmacokinetics; Pulmonary exacerbation