[Drug interactions between nonsteroidal anti-inflammatory drug and pazufloxacin mesilate, a new quinolone antibacterial agent for intravenous use: convulsions in mice after intravenous or intracerebroventricular administration].
Convulsant activity of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, in combination with nonsteroidal anti-inflammatory drug (NSAID) was investigated in mice after intravenous or intracerebroventricular administration. Following results were obtained. 1. In combination with 4-biphenylacetic acid (BPAA) at an oral dose of 100 mg/kg, PZFX mesilate did not induce any convulsions at intravenous doses up to 200 mg/kg. Reference quinolones induced convulsions at the following intravenous doses: Enoxacin (ENX), 3.13 mg/kg or more; norfloxacin (NFLX) and lomefloxacin (LFLX), 6.25 mg/kg or more; ciprofloxacin (CPFX), 50 mg/kg or more; sparfloxacin (SPFX) and temafloxacin (TMFX), 100 mg/kg or more; fleroxacin (FLRX), 200 mg/kg. 2. PZFX mesilate at an intravenous dose of 50 mg/kg did not induce convulsions in mice after oral administration of any of 14 kinds of NSAIDs. It induced convulsions at 200 mg/kg in combination with aspirin at an oral dose of 600 mg/kg, while it did not with the other 13 kinds of NSAIDs. 3. Convulsion-inducing dose of PZFX mesilate after intracerebroventricular administration was 100 mg/body, which was higher than those of reference quinolones (NFLX, CPFX, ENX, LFLX, TMFX, levofloxacin, ofloxacin, FLRX and SPFX) and beta-lactam antibiotics (penicillin G, cefazoline, imipenem/cilastatin and panipenem/betamipron). In addition, concurrent dosing of BPAA (1 microgram/body) did not reduce the convulsion-inducing dose of PZFX mesilate. These results suggest that PZFX mesilate has remarkably weak convulsant activity.
Research Laboratories, Toyama Chemical Co. Ltd., 2-4-1 Shimookui, Toyama 930-8508, Japan.
Hitoshi
H
Fukuda
Yasuhito
Y
Kawamura
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000633:toxicity; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000633:toxicity; D002437:Cefazolin / Q000008:administration & dosage / Q000633:toxicity; D015377:Cilastatin / Q000008:administration & dosage / Q000633:toxicity; D000077728:Cilastatin, Imipenem Drug Combination; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000633:toxicity; D003292:Convulsants / Q000008:administration & dosage* / Q000633:toxicity; D004338:Drug Combinations; D004347:Drug Interactions; D015365:Enoxacin / Q000008:administration & dosage / Q000633:toxicity; D016576:Fleroxacin / Q000008:administration & dosage / Q000633:toxicity; D024841:Fluoroquinolones; D015378:Imipenem / Q000008:administration & dosage / Q000633:toxicity; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009643:Norfloxacin / Q000008:administration & dosage / Q000633:toxicity; D010078:Oxazines / Q000008:administration & dosage* / Q000633:toxicity; D010400:Penicillin G / Q000008:administration & dosage / Q000633:toxicity; D015363:Quinolones / Q000008:administration & dosage / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced; D013845:Thienamycins / Q000008:administration & dosage / Q000633:toxicity; D015091:beta-Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D003292:Convulsants; D004338:Drug Combinations; D024841:Fluoroquinolones; D010078:Oxazines; D015363:Quinolones; D013845:Thienamycins; D015091:beta-Alanine; C075316:panipenem-betamipron; D015377:Cilastatin; C054745:temafloxacin; C023626:4-ethynylbiphenyl; D015365:Enoxacin; C078052:pazufloxacin; D002939:Ciprofloxacin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D002437:Cefazolin; C053091:lomefloxacin; D009643:Norfloxacin; D016576:Fleroxacin; D010400:Penicillin G; C061363:sparfloxacin