PT  - JOURNAL ARTICLE
AU  - Mitsuo Murata
AU  - Ikumi Tamai
AU  - Yoshimichi Sai
AU  - Osamu Nagata
AU  - Hideo Kato
AU  - Akira Tsuji
TI  - Carrier-Mediated Lung Distribution of HSR-903, a New Quinolone Antibacterial Agent
DP  - 1999 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 79--84
VI  - 289
IP  - 1
4099  - http://jpet.aspetjournals.org/content/289/1/79.short
4100  - http://jpet.aspetjournals.org/content/289/1/79.full
SO  - J Pharmacol Exp Ther1999 Apr 01; 289
AB  - HSR-903 [(S)-(−)-5-amino-7-(7-amino-5-azaspiro[2.4]hept-5-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid methanesulfonate] is a newly synthesized quinolone with a potent antibacterial activity and a low toxicity. The lung concentration of unchanged HSR-903 was about nine times higher than that in plasma after oral administration (5 mg/kg) in rats. In comparative studies, HSR-903 was accumulated more efficiently than levofloxacin, ciprofloxacin, and lomefloxacin in rat lung. To clarify the mechanism of the specific distribution of HSR-903 into the lung, the uptake of [14C]HSR-903 was studied using isolated rat lung cells and an isolated rat lung perfusion technique. Initial uptake of HSR-903 by isolated lung cells was temperature dependent, saturable, stereospecific, and Na+ and Cl− dependent. The Hill coefficients (1.90 for Na+ and 1.13 for Cl−) suggest that two Na+ and one Cl− are associated with the transport of one HSR-903 molecule. The uptake of HSR-903 was inhibited by other quinolone antibacterial agents, grepafloxacin, and sparfloxacin. The extraction ratio of HSR-903 in isolated lung perfusion was temperature dependent and saturable. These findings suggest that HSR-903 is taken up by the lung cells via a carrier-mediated transport mechanism, resulting in a concentrative distribution into the lung. The American Society for Pharmacology and Experimental Therapeutics