Pharmacokinetics and Tissue Penetration of the New

A single 400-mg oral dose of grepafloxacin (OPC-17116) was given to each of six healthy male volunteers, and the concentrations of the drug in plasma, cantharides-induced inflammatory fluid, and urine were measured over the subsequent 12 h. The mean peak concentration in plasma of 1.5 mg/ml was attained at a mean time of 2.0 h postdose. The mean peak concentration in inflammatory fluid of 1.1 mg/ml was attained at a mean time of 4.8 h postdose. The mean elimination half-life in plasma was 5.2 h, and that in inflammatory fluid was 12.7 h. The overall penetration into inflammatory fluid was 180.6 % (or 133 % if one aberrant result from one volunteer is excluded). Recovery of the drug in urine during the first 24 h postdose was 8.3 % of the adminis-tered dose. Our results indicate that a once- or twice-daily dosage of grepafloxacin should be adequate to treat systemic infections caused by most bacterial pathogens. Grepafloxacin (OPC-17116) is a new, oral fluoroquinolone which is characterized as having an N-1 cyclopropyl group, a C-5 methyl group, and a C-7 piperazinyl moiety to which a 3-methyl group is attached. In vitro studies suggest that in comparison with the earlier quinolones, grepafloxacin has en-hanced activity against gram-positive cocci, including Strepto