Pharmacokinetics of intravenous finafloxacin in healthy volunteers [PublishAheadOfPrint]

Background: Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad spectrum antibacterial profile. The present study assessed pharmacokinetic properties and safety/tolerability following intravenous infusions.

Methods: In this mixed parallel group/crossover study, healthy male and female volunteers received single (18 volunteers, 200 to 1000mg) or multiple (40 volunteers, 600 to 1000 mg) ascending doses of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to describe pharmacokinetics using a non-compartmental approach. Standard safety and tolerability data were documented.

Results: Finafloxacin had a volume of distribution of 90-127 L (range) at steady state and of 446-550 L at pseudo-equilibrium, indicating the elimination of a large fraction before reaching pseudo-equilibrium. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg*h/mL, 2.56 to 20.2 μg/mL), t_1/2 increased (10.6 to 17.1 h) and urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1000 mg). Pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. Pharmacokinetic parameters were similar for single and multiple administrations. Between-subject variability of exposure ranged from 10% (≤600mg) to 38% (>600mg) (CV%). Adverse events were mild and non-specific, with no dependency on dose or treatment (including placebo).

Conclusions: Despite a relatively high inter-individual variability at higher doses, exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety/tolerability profile.

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