Drug-Drug Interactions (886)

Drug-Drug Interactions (886)
Clinically important drug-drug interactions may occur with coadministration of a quinolone with an aluminum- or magnesium-containing antacid, theophylline, or caffeine. When coadministered with an aluminum- or magnesium containing antacid, oral bioavailability of norfloxacin (553), ciprofloxacin (231, 290, 350,
598), ofloxacin (352, 475), and perhaps all quinolones is substantially diminished, possibly by binding of quinolone to antacid. Peak serum concentrations decreased 16-fold for ciprofloxacin and 4-fold for ofloxacin (352). Sucralfate also reduces the absorption of norfloxacin (563) and likely other quinolones. Patients requiring antacid therapy might alternatively be given cimetidine, ranitidine, or a
calcium-containing
The nonsteroidal antiinflammatory agent fenbufen when coadministered with enoxacin has been associated with the development of seizures in patients in Japan (108). This finding in humans correlates with studies in mice in which combinations of fenbufen with quinolones produced seizures at concentrations >10-fold lower than those producing seizures with either drug alone (K. Morikawa, 0. Nagata, S. Kubo, H. Kato, and K. Yamamoto, Program Abstr. 27th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no.255, 1987). The ability of quinolones to displace T-aminobutyric acid from its receptors on rodent synaptic membranes (783) was also potentiated by some nonsteroidal antiinflammatory agents (S. Hori, J. Shimada, A. Saito, T. Miyahara,
S. Kurioka, and M. Matsuda, Program Abstr. 27th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no. 30, 1987). Theophylline also appears to potentiate quinolone inhibition of binding a r-aminobutyric acid analog to receptors on rat brain membranes (681). Patients given fluoroquinolones other than
Enoxacin decreases the hepatic clearance of the R-enantiomer of warfarin, but not the S-enantiomer; there was, however, little alteration in anticoagulant effect because R-warfarin has one-fifth the potency of S-warfarin in humans (772).
Enoxacin does not affect the clearance of phenytoin (189).
Summary(886)
The pharmacokinetic properties of quinolones in combination with their activity in vitro suggest clinical settings in which these drugs are likely to be efficacious.
Norfloxacin concentrations in urine, feces, kidney, and prostatic tissue suggest usefulness for therapy of urinary tract infections, prostatitis, gonorrhea, and bacterial gastroenteritis. Ciprofloxacin, ofloxacin, enoxacin, pefloxacin, fleroxacin, and lomefloxacin are also likely to be efficacious in these settings; in addition, concentrations of these drugs achieved in blood, lung, bone, and other body tissues and fluids often exceed inhibitory concentrations for gram-negative bacteria and certain gram-positive cocci. Although ciprofloxacin is more potent in vitro against gram-negative bacteria, the greater bioavailability and tissue concentrations of ofloxacin, pefloxacin, enoxacin, fleroxacin, and