Population Pharmacokinetics and Pharmacodynamics
Modeling of Oral Levofloxacin
Sutep Jaruratanasirikul MD*, Archan Jaspattananon MD*, Wibul Wongpoowarak MSc**,
Monchana Nawakitrangsan MPharm*, Suriyan Thengyai PhD***, Maseetoh Samaeng MSc*
Affiliation :
* Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
** Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences,
Prince of Songkla University, Hat Yai, Songkhla, Thailand
*** School of Pharmacy, Walailak University, Tha Sala, Nakhon Si Thammarat, Thailand
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 levofloxacin. The predicted CFRs
for a target AUC0-24 /MIC ratio of 125 for E. coli and Klebsiella spp. were 84.25% and 88.81%, respectively for 500 mg
levofloxacin and 86.00% and 91.34%, respectively for 750 mg levofloxacin.
Conclusion : The population PKs of levofloxacin in the present study were similar to the values obtained from the previous
study. Both 500 mg qd and 750 mg qd of oral levofloxacin dosage regimens had a high probability of achieving optimal
impact against S. pneumoniae, but only the 750 mg qd dosage regimen achieved optimal exposure against Klebsiella spp.
Keywords : Pharmacodynamics, Population pharmacokinetics, Levofloxacin, Monte Carlo simulation, Pharmacokinetic/
pharmacodynamic index
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