Grepafloxacin: pharmacokinetics and tissue penetration

Abstract

Pharmacokinetic and tissue penetration studies of grepafloxacin, a new broad-spectrum fluoroquinolone, show that it has useful properties for the treatment of respiratory tract infections. Grepafloxacin has a volume of distribution that is larger than those of many of the other fluoroquinolones and is concentrated in alveolar macrophages, bronchial mucosa and epithelial lining fluid to a greater extent than are certain other fluoroquinolones. Grepafloxacin concentrations achieved in plasma after a 400-mg oral dose are well in excess of those required to inhibit the respiratory pathogens Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. Streptococcus pneumoniae is also covered for most of the dosing interval, but at normal dose levels grepafloxacin might not inhibit Enterococcus faecalis. The maximum plasma concentrations and area under the concentration---time curve achieved with grepafloxacin suggest that it will be effective for the treatment of community-acquired pneumonia and acute exacerbations of chronic bronchitis. The pharmacokinetics of fluoroquinolones are among their most useful properties. The aim of this paper is to demonstrate whether the differences between grepafloxacin and the other fluoroquinolones are of therapeutic significance.

Modeling of Transfer Kinetics at the Serum-Cerebrospinal Fluid Barrier in Rabbits with Experimental Meningitis: Application to Grepafloxacin

“…The model differs from previous population kinetic models in that not only the partition coefficient but also passive diffusion and active trans- We found a high volume of distribution in the peripheral (tissue) compartment. This is consistent with previous studies (8,13,31) and predictions based on the high lipophilicity of the drug. The average partition coefficient is close to the value obtained by descriptive analysis (16.9 versus 16.0%) (14).…”