Davey P G
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
J Antimicrob Chemother. 1988 Sep;22 Suppl C:97-107. doi: 10.1093/jac/22.supplement_c.97.
Drug interactions with the quinolones are of two types: pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions include inhibition of absorption of quinolones by aluminium and magnesium containing antacids and inhibition of metabolism of other drugs by quinolones. Norfloxacin and ofloxacin are not extensively metabolized and do not inhibit drug metabolism; ciprofloxacin and enoxacin reduce theophylline clearance in normal subjects by less than 50% and greater than 50% respectively. Ciprofloxacin inhibits the metabolism of caffeine, theophylline and antipyrine. The latter is a marker of broad substrate specificity and, until proved otherwise, it would be prudent to avoid combination of ciprofloxacin with drugs which are metabolized and have a low therapeutic index. In addition to theophylline, these include cyclosporin, phenytoin and warfarin. There is evidence that the elderly and patients with liver disease are particularly susceptible to kinetic interactions with ciprofloxacin. In contrast, there is no evidence to suggest that ofloxacin is likely to impair hepatic drug elimination. Enoxacin does not impair the metabolism of chlorpropamide or glibenclamide, it is therefore unlikely that any of the quinolones will interact with sulphonylurea hypoglycaemic drugs. A pharmacodynamic interaction has been demonstrated in vitro between quinolones and non-steroidal anti-inflammatory drugs (NSAIDS) or theophylline. All of these drugs inhibit binding of radio-labelled gamma-amino-butyric acid to mouse synaptic membranes and combinations of quinolones with NSAIDS or theophylline are synergistic. Convulsions have been reported in patients who received a combination of enoxacin with either fenbufen, a NSAID, or theophylline. Like theophylline, NSAIDS undergo hepatic metabolism, so the clinical interaction may be the result of combined pharmacokinetic and pharmacodynamic interactions. Drug-interactions with quinolones are a clinically important problem. Drugs, such as ofloxacin, which do not impair hepatic metabolism of other drugs, have a clinically significant advantage over other quinolones. The pharmacodynamic interaction between quinolones and other GABA inhibitors is extremely poorly documented; further in-vitro, animal and clinical studies are urgently required.
药代动力学相互作用和药效学相互作用。药代动力学相互作用包括含铝和镁的抗酸剂抑制喹诺酮类药物的吸收，以及喹诺酮类药物抑制其他药物的代谢。诺氟沙星和氧氟沙星代谢不广泛，不抑制药物代谢；环丙沙星和依诺沙星分别使正常受试者的茶碱清除率降低不到50%和超过50%。环丙沙星抑制咖啡因、茶碱和安替比林的代谢。后者是广泛底物特异性的标志物，在未证实相反情况之前，谨慎做法是避免环丙沙星与经代谢且治疗指数低的药物联合使用。除茶碱外，这些药物还包括环孢素、苯妥英和华法林。有证据表明，老年人和肝病患者特别容易发生与环丙沙星的动力学相互作用。相比之下，没有证据表明氧氟沙星可能损害肝脏药物消除。依诺沙星不损害氯磺丙脲或格列本脲的代谢，因此任何喹诺酮类药物都不太可能与磺酰脲类降糖药物相互作用。喹诺酮类药物与非甾体抗炎药（NSAIDs）或茶碱之间已在体外证明存在药效学相互作用。所有这些药物都抑制放射性标记的γ-氨基丁酸与小鼠突触膜的结合，喹诺酮类药物与NSAIDs或茶碱的组合具有协同作用。有报道称，接受依诺沙星与非甾体抗炎药芬布芬或茶碱联合治疗的患者发生了惊厥。与茶碱一样，NSAIDs也经过肝脏代谢，因此临床相互作用可能是药代动力学和药效学相互作用共同作用的结果。喹诺酮类药物的药物相互作用是一个临床上重要的问题。像氧氟沙星这样不损害其他药物肝脏代谢的药物，在临床上比其他喹诺酮类药物具有显著优势。喹诺酮类药物与其他γ-氨基丁酸抑制剂之间的药效学相互作用记录极少；迫切需要进一步的体外、动物和临床研究。
