Pharmacokinetics of intravenous and oral levofloxacin in critically ill adults in a medical intensive care unit.
OBJECTIVE
To characterize the pharmacokinetic disposition of intravenous and oral levofloxacin in critically ill adults.


METHODS
Prospective, open-label study.


METHODS
University teaching hospital.


METHODS
Thirty critically ill patients in a medical intensive care unit (ICU).


METHODS
All patients received levofloxacin as part of their routine medical care. Pharmacokinetic evaluations were performed in 28 patients receiving intravenous levofloxacin. Ten of these patients subsequently were switched to oral levofloxacin and underwent a second pharmacokinetic evaluation during oral therapy.


RESULTS
Mean +/- SD levofloxacin half-life, clearance at steady state, and volume of distribution in all 28 patients were 8.0 +/- 1.7 hours, 134 +/- 35 ml/minute, and 1.2 +/- 0.3 L/kg, respectively Maximum and minimum serum concentrations (Cmax and Cmin) and area under the serum concentration-time curve from 0-24 hours (AUC(0-24)) in patients receiving levofloxacin 500 mg intravenously were 7.5 +/- 0.8 mg/L, 1.0 +/- 0.5 mg/L, and 66.1 +/- 15.7 mg x hour/L, respectively Observed Cmax, Cmin, and time at which maximum concentration was achieved after oral doses of levofloxacin 500 mg were 5.5 +/- 1.1 mg/L, 0.8 +/- 0.4 mg/L, and 1.3 +/- 0.4 hours, respectively. These values were significantly different (p < 0.05) from those observed after intravenous dosing in the same patients; other pharmacokinetic parameters were similar. Statistically significant increases (p < 0.05) in Cmax, Cmin, half-life, and AUC(0-24) were found in critically ill patients administered multiple doses of intravenous levofloxacin compared with historical data from healthy volunteers.


CONCLUSIONS
The dosage regimen of intravenous levofloxacin 500 mg once/day appears adequate for most pathogens found in critically ill patients with normal renal function. Less susceptible pathogens may require an increased daily dose for more optimal therapy. Orally administered levofloxacin appears to be well absorbed in selected ICU patients and has pharmacokinetics similar to those of intravenously administered levofloxacin.
Rebuck
Jill A
JA
Department of Pharmacotherapy, Fletcher Allen Health Care, University of Vermont, Burlington, USA.
Fish
Douglas N
DN
Abraham
Edward
E
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003404:Creatinine / Q000378:metabolism; D016638:Critical Illness; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007362:Intensive Care Units; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D013997:Time Factors
D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin; D003404:Creatinine