Population Pharmacokinetics and Pharmacodynamics Modeling of Oral Levofloxacin
Abstract
BACKGROUND: Levofloxacin, a fluoroquinolone, is an isomer of ofloxacin with an extensive spectrum of antimicrobial efficacy. In common with other fluoroquinolones, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with its therapeutic efficacy is the area under the plasma time-concentration curve (AUC)/the minimum inhibitory concentration (MIC) ratios.
OBJECTIVE: To evaluate the population PK and determine the efficacy of various dosage regimens in achieving the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of oral levofloxacin when prescribed as the switching therapy after intravenous levofloxacin treatment.
MATERIAL AND METHOD: The PK studies were conducted in 45 healthy volunteers who received one 500 mg tablet of levofloxacin and PTAs were determined by using a Monte Carlo simulation. The dosage regimens were predicted to achieve CFR greater than or equal to 90% by referral to the MIC distributions database of the European Committee on Antimicrobial Susceptibility Testing.
RESULTS: The population PKs of levofloxacin were; the volume of distribution (V) = 101.71±1.41 L, total clearance (CL) = 8.51±1.43 L/hour and the area under the plasma time-concentration curve from 0 to 24 hours (AUC0-24 ) = 66.19±1.30 mg*hour/L. The predicted CFRs for a target AUC0-24 /MIC ratio of 30 for S. aureus and S. pneumoniae were 83.12% and 92.63%, respectively for 500 mg levofloxacin, and 84.96% and 98.17%, respectively for 750 mg…
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