Pharmacokinetic comparison of two levofloxacin 100-mg tablet formulations and determination of time point appropriately reflecting its area under the curve

ABSTRACT

Levofloxacin is a broad-spectrum antibiotic with activity against gram-positive and -negative bacteria. This study compared the pharmacokinetics (PK) and evaluated the bioequivalence of two levofloxacin 100-mg tablet formulations. An open, randomized, two-way crossover study was conducted in 28 healthy volunteers. The reference (Cravit Tab 100-mg, Jeil) or test (Levobacter Tab, Seoul) formulation was administered and serial blood samples were collected over 24 h for PK analysis. Levofloxacin plasma concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The correlation of levofloxacin concentration at various time points with the area under the concentration time-curve over the time interval from 0 extrapolated to infinity (AUCinf) was estimated to determine the best reflected time point. The average half-life, maximum plasma concentration (Cmax), and AUClast were comparable. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR test/reference) of AUClast and Cmax were 0.8200-1.0633 and 0.9474-1.0643 respectively. Both formulations were tolerated with no clinically relevant safety issues. Plasma levofloxacin concentrations at various time points correlated well with the AUCinf, and showed high correlation coefficients (r > 0.7, P < 0.001) for both drugs 8 and 12 h after administration. Both formulations showed similar PK profiles while levofloxacin plasma levels after administration indicated their bioequivalence. The Cmax and AUClast GMR 90% CIs were 0.80-1.25. Moreover, 12 h was the best time point to predict the AUCinf and therefore suitable for therapeutic drug monitoring.