NEURO EXCITABILITY OF SPARFLOXACIN, A NOVEL QUINOLONE ANTIBACTERIAL DRUG, IN COMBINATION WITH NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

• Published in: CHEMOTHERAPY Vol. 39; no. Supplement4; pp. 167 - 174
• Main Authors: Nozaki, Masakatsu, Tanaka, Kazuhiko, Takeda, Noriaki, Niwa, Masayuki, Kohno, Kenichi, Kobayashi, Motohiro, Tsurumi, Kaito
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 28.08.1991
• Subjects: Sparfloxacin
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.39.Supplement4_167

Sparfloxacin (SPFX), a novel quinolone antibacterial (NQ) was compared with other NQs such as norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX), lomefloxacin (LFLX) and tosufloxacin-tosilate (TFLX) on the central nervous system (CNS) exitability in combination with, or without, non-steroidal anti-inflammatory drugs (NSAID) in mice. Intraperitoneal administration of large doses of NQs except SPFX caused convulsant death. LD50 values (mg/kg) of NQs were 700 for LFLX, 805 for OFLX, 1064 for NFLX, 1165 for CPFX, 3600 for ENX and 3100 for SPFX, respectively. These neuroexcitable effects of NQs were amplified by concomitant administration of 4-biphenylacetic acid (BPAA), an active metabolite of fenbufen, resulting in tonic and clonic convulsions and convulsant death. The rank order was ENX<NFLX<LFLX<CPFX<OFLX<SPFX on the basis of dose. when NQs other than SPFX were orally given in combination with BPAA, ketoprofen or naproxen, convulsions were induced in a dose dependent manner. As to the convulsive effects of NQs with 200mg/kg BPAA: a dose (mg/kg) which caused convulsive death in all animals was 50 for LFLX, 75 for ENX, 200 for NFLX, 400 for CPFX and 1500 for OFLX, respectively. Concomitant use of 1500mg/kg TFLX and 400mg/kg BPAA evoked convulsions in 10% animals. In contrast, no neuroexitable activity and convulsions were observed in the oral intake of SPFX under all experimental conditions. In the presence or absence of BPAA, SPFX showed no affinity against GABAA receptor. These results suggest that SPFX possesses little neuro-excitability and that SPFX appears to have exceptional ability to avoid the CNS-related adverse reactions induced by concomitant use of NSAID and NQs.