Influence of subject age on the inhibition of oxidative metabolism by ciprofloxacin

Abstract

Case reports suggest that the magnitude of inhibition of oxidative metabolism produced by ciprofloxacin may be greater in elderly subjects. We examined the effect of oral ciprofloxacin on antipyrine disposition in 13 young (ages, 23 to 34 years) and 9 elderly (ages, 65 to 82 years) healthy volunteers. Ciprofloxacin decreased antipyrine oral clearance in young and elderly subjects (P < 0.05), with the average decreases being similar in both groups (23.3% for the young subjects and 27.9% for the elderly subjects). Ciprofloxacin concentrations in serum were significantly higher (mean, 57%) in the elderly. The formation clearance of 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was also significantly decreased in both groups of subjects; however, norantipyrine formation, accounting for 15 to 20% of antipyrine clearance, was reduced only in the elderly. These results suggest that elderly subjects are not more sensitive to the inhibitory effect of ciprofloxacin on antipyrine metabolism. However, careful clinical monitoring is necessary with all patients, irrespective of age, taking ciprofloxacin concomitantly with drugs primarily eliminated by the cytochrome P-450 system.Ciprofloxacin is a fluoroquinolone antibiotic with widespread therapeutic application because of its broad spectrum of antibacterial activity, oral effectiveness, and low incidence of serious adverse effects. Studies over the past few years have established that several fluoroquinolones, including ciprofloxacin, inhibit the oxidative hepatic metabolism of a number of substrates (3). Most of these studies have involved young healthy volunteers. However, case reports and a retrospective study suggest that the magnitude of inhibition may be greater in elderly subjects. Raoof et al. (12) evaluated the effect of ciprofloxacin on theophylline concentrations in 33 hospitalized patients and found that the patients who experienced significant increases in theophylline concentrations were older than those.who did not. Case reports by Rybak et al. (15) and Thomson et al. (19) described elderly patients (82 and 92 years of age, respectively) with therapeutic (10 to 15 mg/liter) theophylline concentrations who experienced increases to more than 30 mg/liter after starting therapy with ciprofloxacin. Estimated theophylline clearance decreased by 56 and 64%, respectively, in these reports, substantially greater than the average decrease of 15 to 30%o observed in studies with young healthy volunteers (9,11,17).In addition to the possibility of an enhanced inhibitory response to ciprofloxacin in the elderly, drug interactions are more likely in this age group as a result of the large number of medications consumed. Therefore, the purpose of this study was to prospectively test the hypothesis that the magnitude of inhibition of oxidative metabolism produced by ciprofloxacin is greater in elderly than in young individuals by comparing effects on the disposition of antipyrine and its major metabolites. MATERIALS AND METHODS Subjects. Thirteen young healthy volu...

Quinolones

“…Gatifloxacin does not significantly alter the pharmacokinetics of intravenous midazolam [250]. Waite and coworkers demonstrated that elderly subjects are not more sensitive than younger subjects to the inhibitory effect of ciprofloxacin on hepatic metabolism of antipyrine [251]. Similarly, Loi and coworkers demonstrated that elderly subjects are not more sensitive to the inhibitory effect of ciprofloxacin on hepatic metabolism of theophylline [252].…”

Quinolone Antibacterials

“…treatment compared with the administration before ciprofioxacin treatment. No effect of age on the inhibition of antipyrine metabolism by ciprofioxacin was seen (WAITE et al 1991). In contrast, a pronounced inhibitory effect on the hydroxylation of antipyrine was found after a single dose of 400mg enoxacin (BOETTCHER and WOLTER 1989).…”