Vol.55 No.S-1 October 2007
Pharmacokinetics of garenoxacin in laboratory animal species
Research Laboratories, Toyama Chemical Co., Ltd., 2-4-1, Shimookui, Toyama, Japan
Abstract
The pharmacokinetics of a novel des-fluoro(6)-quinolone antibacterial agent, garenoxacin mesilate hydrate(GRNX), was investigated using several laboratory animal species. GRNX was rapidly absorbed and widely distributed into most tissues/organs except the cerebrum and spinal cord. Radioactivity was completely excreted from the body after the administration of [14C] GRNX in rats and monkeys, suggesting low persistence of GRNX. The linearity of systemic exposure on laboratory animal species was suggested among the dose range tested in this study (rats: 2 to 25 mg/kg, dogs: 8 to 75 mg/kg, and monkeys: 25 to 100 mg/kg). The in vitro serum protein binding of GRNX was consistent in GRNX concentrations tested on mice, rats, dogs, monkeys, and humans (mice: 66.7 to 71.9%, rats: 86.5 to 89.0%, dogs: 64.5 to 67.6%, monkeys: 71.2 to 74.5%, and humans: 78.3 to 84.0%). The urinary recovery of GRNX in rats decreased with increasing dose. However, that in dogs was consistent at each dose; species difference was observed in the urinary excretion of GRNX. Systemic exposure of GRNX in female rats was lower than that in male rats (about 33% of AUC0-∞ in male), the gender difference was observed. No gender difference was observed in biliary and urinary excretion of radioactivity. One of the reasons for the gender difference in systemic exposure of GRNX is GRNX metabolism.
Key word
garenoxacin, absorption, tissue penetration, protein binding, excretion
Received
April 27, 2007
Accepted
July 18, 2007
Jpn. J. Chemother. 55 (S-1): 78-86, 2007
