[Mechanism of renal excretion of T-3761, a novel fluoroquinolone agent, in rabbits].
The mechanism of the renal excretion of T-3761, a novel oral fluoroquinolone agent, was studied by renal clearance, stop-flow techniques and analyzing the pharmacokinetics with and without probenecid in rabbits, and which were compared with those of ofloxacin (OFLX). In rabbits probenecid treatment induced increases in the elimination half-life (2.1 times higher) and area under the serum concentration-time curve (3.1 times), and decreases in elimination rate constant (0.44 times) and total body clearance (0.35 times), while volume of distribution showed no significant change. In the stop-flow pattern, a specific peak of T-3761 was observed. On the other hand, a peak of OFLX was observed at the peak of PAH and a small trough at the trough of sodium. And the renal clearance of T-3761 and OFLX were about 4.9 and 3.3 times higher than the corresponding Clcr, respectively. These results suggested that T-3761 was excreted into urine by both glomerular filtration and renal tubular secretion, and was scarcely reabsorbed at distal tubule. The short elimination half-life of T-3761 might be explained by its great ratio of tubular excretion.
Fukuda
Y
Y
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Muratani
T
T
Takahata
M
M
Fukuoka
Y
Y
Yasuda
T
T
Watanabe
Y
Y
Narita
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D024841:Fluoroquinolones; D006207:Half-Life; D007668:Kidney / Q000378:metabolism*; D008297:Male; D015242:Ofloxacin / Q000493:pharmacokinetics; D010078:Oxazines / Q000493:pharmacokinetics*; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010078:Oxazines; C078052:pazufloxacin; D015242:Ofloxacin; D011339:Probenecid