RT Journal Article
SR Electronic
T1 METABOLISM AND DISPOSITION OF NOVEL DES-FLUORO QUINOLONE GARENOXACIN IN EXPERIMENTAL ANIMALS AND AN INTERSPECIES SCALING OF PHARMACOKINETIC PARAMETERS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1409
OP 1418
DO 10.1124/dmd.31.11.1409
VO 31
IS 11
A1 Hayakawa, Hiroyoshi
A1 Fukushima, Yoko
A1 Kato, Hiroshi
A1 Fukumoto, Hiroyuki
A1 Kadota, Takumi
A1 Yamamoto, Hiroyuki
A1 Kuroiwa, Hiroyuki
A1 Nishigaki, Junko
A1 Tsuji, Akira
YR 2003
UL http://dmd.aspetjournals.org/content/31/11/1409.abstract
AB Garenoxacin is a novel quinolone that does not have a fluorine substituent at the C-6 position in the quinoline ring. Garenoxacin or14C-garenoxacin was intravenously or orally administered to rats, dogs, and monkeys. Metabolic profiles and pharmacokinetic parameters were investigated focusing on the species differences and the allometric scaling of pharmacokinetic parameters. Garenoxacin was well absorbed following oral administration then underwent phase II metabolism in all species tested. Major metabolites of garenoxacin were the sulfate of garenoxacin (M1) and glucuronide (M6). Oxidative metabolites were present in very minor concentrations in all species tested. Another minor route of metabolism was the formation of the carbamoyl glucuronide. Garenoxacin is characterized across species by the observation that it circulates systemically, is excreted renally as unchanged drug, and is metabolized to M1 and M6, which are excreted specifically into the bile. The total clearances (CL) were 12.1, 2.43, and 3.39 ml/min/kg for rats, dogs, and monkeys, respectively. The distribution volume values of garenoxacin (Vss) were 0.88, 1.29, and 0.96 l/kg for rats, dogs, and monkeys, respectively. In all animals tested, the extrarenal clearance was larger than the renal clearance, and neither of the clearances was limited by blood flow. Despite these conditions, garenoxacin showed a good correlation for CL and Vss for allometric interspecies scaling. The American Society for Pharmacology and Experimental Therapeutics