JAC Advance Access published online on October 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg468
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Centre for Pharmaceutical
Research, School of Pharmaceutical, Molecular and Biomedical Sciences,
University of South Australia, Adelaide
* Corresponding author. E-mail: coulthardk{at}wch.sa.gov.au.
Received 27 March 2003
; revised 5 August 2003
; accepted 9 September 2003
Objectives: To define the steady-state
pharmacokinetics of colistin methanesulphonate and colistin in patients
with cystic fibrosis (CF) following intravenous administration of
the former. Materials and methods: The study was conducted
in 12 patients with CF following intravenous administration of colistin
methanesulphonate (1.63-3.11 mg/kg) every 8 h for at least
2 days. On the day of study, four blood samples were collected from
each patient at 60, 120, 240 and 360 min after the end of the infusion. Concentrations
of colistin methanesulphonate and colistin in plasma were measured
separately by HPLC. Results: At steady-state, colistin methanesulphonate
had a mean (± S.D.)
total body clearance, volume of distribution and half-life of
2.01 ± 0.46 mL/min per kg, 340 ± 95
mL/kg and 124 ± 52 min, respectively.
Colistin had a significantly longer mean half-life of 251 ± 79
min (P < 0.001). With the regimen used,
colistin methanesulphonate was well tolerated. This is the first
report on the pharmacokinetics of colistin methanesulphonate in
CF patients determined using concentrations of colistin methanesulphonate
and colistin in plasma. Conclusions: Based on the in vitro pharmacodynamics
against Pseudomonas aeruginosa previously published
by our group and these pharmacokinetic findings, dose escalating
trials may be warranted to maximize efficacy.
Keywords: colistin, HPLC, pharmacodynamics, Pseudomonas
Steady-state pharmacokinetics of intravenous colistin methanesulphonate
in patients with cystic fibrosis
2 Centre for Pharmaceutical
Research, School of Pharmaceutical, Molecular and Biomedical Sciences,
University of South Australia, Adelaide; Department of Pharmacy, Women’s
and Children’s Hospital, North Adelaide, SA 5006, Australia;
3 Regional Adult Cystic Fibrosis
Unit, Seacroft Hospital, Leeds, UK
4 Department of Microbiology and Infectious Diseases, Women’s
and Children’s Hospital, North Adelaide, SA 5006, Australia;
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