JAC Advance Access published online on September 6, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf168
© 2002 by The British Society for Antimicrobial Chemotherapy
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Original Paper
1 School of Pharmacy, University
of Southern California, Los Angeles, CA
* Corresponding author. E-mail: beringer{at}usc.edu.
Received 18 January 2002
; revised 5 June 2002
; accepted 3 July 2002
Aminoglycosides are often prescribed as part of the
treatment regimen for acute pulmonary exacerbations due to their
potent activity and low potential for development of resistance. Preliminary
evidence from randomized controlled trials in patients with cystic
fibrosis (CF) suggests that once-daily administration of aminoglycosides
results in similar efficacy and a low risk for toxicity compared
with traditional dosing. The pharmacokinetics of aminoglycosides administered
once daily in CF patients are currently not well described. In this
study we compare the distribution and elimination patterns of traditional
dosing (3.3 mg/kg q8h) versus once-daily dosing (10 mg/kg q24h)
of tobramycin in six adult patients with CF. The pharmacokinetics
of tobramycin administered either once daily or every
8 h were best described by a two-compartment model. No statistically
significant differences in any of the pharmacokinetic parameter
values between regimens were noted. The distribution phase half-lives
of 32 and 24 min following the q8h and q24h regimens were longer
than expected. The use of a one-compartment model requires clinical
peak levels to be drawn 2 h after initiation of either a 30 min
infusion for multiple daily dosing or a 60 min infusion with once-daily
dosing, to ensure completion of the distribution phase. Our data
indicate that a dose of 10 mg/kg/day provides post-distributional phase
peak concentrations that achieve the desired goal for susceptible
organisms (>20 mg/L) and AUC24 values at the
upper end of the desired range (70-100 mg·h/L).
Distribution and elimination of tobramycin administered
in single or multiple daily doses in adult patients with cystic
fibrosis
2 School of Pharmacy, University
of Southern California, Los Angeles, CA; Laboratory of Applied
Pharmacokinetics, University of Southern California, Los Angeles,
CA USA; USC Adult
Cystic Fibrosis Center, University of Southern California, Los Angeles,
CA
3 Keck
School of Medicine, University of Southern California, Los Angeles,
CA, USA
4 Laboratory of Applied
Pharmacokinetics University of Southern California, Los Angeles,
CA, USA; Keck
School of Medicine, University of Southern California, Los Angeles,
CA, USA
5 USC Adult
Cystic Fibrosis Center, University of Southern California, Los Angeles,
CA, USA; Keck
School of Medicine, University of Southern California, Los Angeles,
CA, USA
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