Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis

Chest. 1997 Nov 5;112(5):1208-13. doi: 10.1378/chest.112.5.1208.

Abstract

Study objective: Tobramycin is commonly used to treat respiratory tract infections in patients with cystic fibrosis. We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobramycin in this population.

Design: Multiple blood samples were collected from each patient, and serum concentrations of tobramycin were determined by a fluorescence polarization immunoassay. Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audiometric evaluations were performed at the start and end of therapy.

Measurements and results: Eighteen patients (mean age, 24.6 years) received tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion over 20 min. The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L. A mean dose of 11.9+/-1.9 mg/kg was needed to obtain a theoretical mean peak serum concentration of 42.4+/-4.5 mg/L. The mean total body clearance, apparent volume of distribution, and elimination half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively. The period of time that the serum concentration exceeded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer compared with the use of divided daily doses in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient.

Conclusion: Based on our data, tobramycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Child
  • Cost-Benefit Analysis
  • Cystic Fibrosis / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Evaluation
  • Female
  • Fluorescence Polarization Immunoassay
  • Half-Life
  • Humans
  • Length of Stay
  • Male
  • Respiratory Tract Infections / drug therapy
  • Safety
  • Tobramycin / administration & dosage
  • Tobramycin / pharmacokinetics*
  • Tobramycin / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Tobramycin