新キノロン薬と抗炎症薬併用により誘発されるけいれん

Abstract

A0dministration of a large doses (500-3, 000mg/kg, i.p.) of new quinolone antibacterials (NQs) such as norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX) and lomefloxacin (LFLX) caused convulsant death in mice. LD50 values (mg/kg) of NQs were 698 for LFLX, 805 for OFLX, 1064 for NFLX, 1165 for CPFX and 3600 for ENX, respectively. These neuroexitable effects of NQs were amplified by concomitant intake of 4-biphenylacetic acid (BPAA) as an active metabolite of fenbufen, keto-profen and naproxen, resulting in tonic and clonic convulsions and convulsant death. In this case, the order of the dose of NQ on inducing convulsion was expressed as follows; ENX<LFLX<NFLX<CPFX<OFLX. The CNS activity of NQ, except CPFX, was amplified by naproxen, more significantly than by ketoprofen. CPFX was sensitive to ketoprofen. ENX in the presence of NSAID demonstrated an affinity for GABA receptor.Thus, GABA-ergic mechanism may be responsible for the effect of NSAID on the CNS activity of NQ. However, it was difficult to find a certain relation between inhibition of GABA binding and convulsion.