Pharmacokinetics of prulifloxacin. 1st communication: absorption, distribution and excretion in rats, dogs and monkeys after a single administration.

The pharmacokinetics of prulifloxacin ((+/-)-6-fluoro-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-car boxylic acid. CAS 123447-62-1, NM441), a quinolone antibacterial prodrug, was investigated after i.v. (14C-NM394, CAS 112984-60-8) or oral (14C-NM441) administration to rats, dogs and monkeys. 1. 14C-NM441 was absorbed mainly from the upper small intestine and then metabolized to NM394 partly in the intestinal membrane but mainly in the portal blood and liver. Thus NM441 was not detected in the systemic circulation. 2. After i.v. administration of 14C-NM394 (5 mg/kg), the plasma concentration of radioactivity decreased biexponentially, and the elimination half-life in rats, dogs and monkeys was 4.2, 5.8 and 7.0 h, respectively. After oral administration of 14C-NM441 (20 mg/kg), the plasma concentration of radioactivity reached a maximum at 0.7-3.3 h, and thereafter decreased as observed after i.v. administration of 14C-NM394. An effect of food on the absorption of NM441 was found. No clear sex-related differences were observed in the plasma concentration profiles of rats. 3. The concentration of radioactivity in most tissues of rats reached a maximum within 1 h after oral administration of 14C-NM441 and thereafter decreased along with the plasma concentration. At 0.5 h, the radioactivity concentrations were highest in the liver and kidney, moderately high in the spleen, pancreas, lung and mandibular gland and extremely low in the cerebrum and cerebellum. 4. The radioactivity in the excreta collected over a 96-h period was 96-98% of the oral dose (urine, 22-32%; feces, 64-75%) in rats, dogs and monkeys, 35% of the radioactivity administered was excreted in the bile of rats during a 48-h period after oral administration, and only a small portion of the biliary radioactivity was reabsorbed. 5. The proportion of 14C-NM394 that bound to serum proteins in vitro in rats, dogs, monkeys and humans was 41-59% in a concentration range of 0.1-10 micrograms/ml.