Study of the convulsive phenomenon induced by new quinolones

最近，我们得知一些患者在服用抗炎药芬布芬的同时口服了一种新的喹诺酮类药物依诺沙星，出现了惊厥。这项研究是由我和我的同事进行的，在各种实验动物中研究一些新的喹诺酮类药物，如依诺沙星，诺氟沙星，氧氟沙星和其他类似的新化合物的中心作用。这些药物单独使用没有明显的中枢作用，然而，非甾体抗炎药芬布芬与新型喹诺酮类药物联合使用可产生典型脑电波模式的癫痫样发作。小鼠、大鼠、兔子、猫甚至青蛙都出现了抽搐。此外，痉挛是由多种给药途径引起的，如p.o.、i.v.、i.m.、i.p.等。不幸的是，到目前为止还没有发现抗惊厥药物，但地西泮和其他一些苯二氮卓类药物能在相对短的时间内抑制惊厥。在非甾体抗炎药中，芬布芬是一种强效增强剂。此外，许多研究者报道氟比洛芬、萘普生、吩洛芬Ca、普拉洛芬等也可引起新型喹诺酮类药物的惊厥。Wijnands等人（1984）已经报道了依诺沙星可提高茶碱的血浆浓度，但在其他新型喹诺酮类药物中尚未发现这一现象。反正抽搐严重，不能同时开新的喹诺酮类药物和非甾体类抗炎药。

Recently, we are informed that some patients who received orally a new quinolone, enoxacin at the same time as fenbufen that is an antiinflammatory drug, showed convulsion. The study was performed by myself and my coworkers, in various experimental animals to investigate the central action of some new quinolones such as enoxacin, norfloxacin,ofloxacin and other similar new compounds. These drugs in single usage showed no significant central action, comp however, a combination of a non-steroidal antiinflammatory drug, fenbufen, with the new quinolones produced epilepti-form seizure with typical brain wave pattern. The convulsions were seen in mice, rat, rabbits, cats and even in frogs. Further the convulsion was produced by many routes of administrations, such as p.o., i.v., i.m., i.p. etc. Unfortunately, no anticonvulsant drugs have been found so far, but diazepam and some other benzodiazepines suppressed the convulsion for relatively short period.Among the nonsteroidal antiinflammatory drugs, fenbufen is a powerful potentiator. Further, many researchers have reported that flurbiprofen, naproxen, phenoprofen Ca, pranoprofen etc. also elicit the convulsion of new quinolones.Wijnands et al, (1984) already reported that enoxacin raises plasma concentrations of the theophylline, but this phenomenon is not found in other new quinolones, so far.Anyway, the convulsion is serious, and the combination of new quinolones and nonsteroidal antiinflammatory drugs must not be prescribed.