Overview of drug interactions with the quinolones

Abstract

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.