Pharmacokinetics of the new fluoroquinolone balofloxacin in mice, rats, and dogs.
The pharmacokinetics of 1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline -3-carboxylic acid dihydrate (CAS 127294-70-6, balofloxacin, Q-35), a new fluoroquinolone, were studied in mice, rats and dogs by high performance liquid chromatography. The mean oral bioavailabilities of balofloxacin calculated from the area under the curve after oral and intravenous administration in mice, rats and dogs were 19.03, 87.50 and 87.73%, respectively, indicating that balofloxacin was almost completely absorbed in rats and dogs but not in mice after single oral administration. The mean elimination half-lives in plasma after intravenous administration in mice, rats and dogs were 0.92, 1.33 and 6.38 h, respectively. Mean cumulative urinary excretion percentages of unchanged balofloxacin within 24 h of oral administration of balofloxacin at the dose of 20 mg/kg in mice, rats and dogs were 4.91, 21.77 and 22.49% of the dose, respectively. A small portion of the metabolite was excreted into urine as balofloxacin glucuronide and N-desmethyl balofloxacin in these species. After oral administration of balofloxacin at the dose of 100 mg/kg to rats, absorption was prolonged compared with that after administration at the doses of 5 and 20 mg/kg. Plasma concentration-time profiles and pharmacokinetic parameters of balofloxacin in male rats were similar to those in female rats, indicating no sex-related differences. Once daily 21-day multiple administrations had not affect on these pharmacokinetic profiles of balofloxacin in rats.
Nakagawa
T
T
Drug Metabolism and Pharmacokinetics Research Laboratory, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Ishigai
M
M
Kato
M
M
Hayakawa
N
N
Kinoshita
H
H
Okutomi
T
T
Ohkubo
K
K
Okazaki
A
A
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D004285:Dogs; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C077155:balofloxacin