Disposition of Q-35(2): Distribution after Single and Repeated Oral Administration of ¹⁴C-Q-35 in Rats

Abstract

The distribution of radioactivity after a single and repeated oral administration of ¹⁴C labeled Q-35[(±)-1-cyclopropyl-6-fluoro-1, 4 dihydro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline-3-carboxylic acid], a new fluoroquinolone antimicrobial agent, was studied in rats.
1. The levels of the radioactivity in most tissues reached their maximum at 30 min after a single oral administration of ¹⁴C-Q-35 at the dose of 20 mg/kg. The peak levels of radioactivity in all tissues except, brain, eyeball and fat, were higher than those observed in plasma. The radioactivity distributed rapidly and well to many tissues, and there was a rapid elimination of radioactivity from these tissues.
2. In the tissues, to which a high degree of radioactivity distributed, the total radioactivity consisted mostly of unchanged Q-35 and of small quantities of metabolites. It was suggested that almost all Q-35 administered distributed to various tissues and was remaining as an unchanged form without metabolism.
3. During 14 days repeated administration, the tissue levels of radioactivity were nearly similar to those after first administration, and the excretion rates of radioactivity into the urine and feces were nearly constant.
Tissue levels of radioactivity after the 14th administration decreased rapidly in parallel with the plasma level. Neither an accumulation nor a residue of radioactivity was obserbed.