Disposition and metabolism of [14C]sparfloxacin after repeated administration in the rat.

Disposition and metabolism of [carbonyl-14C]sparfloxacin (SPFX, 5-amino-1-cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro- 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, AT-4140; CAS 110871-86-8), a novel antimicrobial quinolone, were studied in rats during and after 14 consecutive daily oral administrations at 10 mg/kg. Plasma levels after the 1st and 14th administration were similar in terms of tmax (1 h), Cmax (around 1.35 micrograms eq/ml), T1/2 (3-4 h) and AUC (about 7.3 micrograms eq h/ml). Plasma levels at 0.5 h after each administration were virtually constant in the range of 1.25-2.66 micrograms eq/ml for 14 days, but those at 24 h tended to elevate to about 0.06 micrograms eq/ml, which was an apparent steady state level after the 6th administration. Tissue distribution after the repeated administration was also similar to that after single administration: levels in the kidney, liver, pancreas, submaxillary gland, lung and many others were higher than, or similar to those in plasma, and in brain and some others, lower. Composition of radioactive metabolites in urine was not statistically different from that after single administration. About 20 and 73% of dose were excreted in daily urine and feces, respectively, for 14 days and radioactivity was almost completely excreted within 96 h after the last administration.