Enoxacin decreases the clearance of theophylline in man.

Abstract

In patients treated concurrently with theophylline and enoxacin, a new broad‐spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/‐ s.d. theophylline concentrations increased from 8.5 +/‐ 2.8 micrograms ml‐1 prior to enoxacin to a maximum of 21.7 +/‐ 7.8 micrograms ml‐1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/‐ 2.4 micrograms ml‐1 prior to enoxacin treatment to 15.0 +/‐ 5.1 micrograms ml‐1 at day 3 of coadministration (P less than 0.005). Plasma protein‐binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended.

Comparison of Inhibitory Effects of New Quinolones on Drug Metabolizing Activity in the Liver

“…The in vivo experiments in this study showed that ENX markedly and NFLX slightly prolonged the T1 /2 of theophylline in rats, but OFLX did not affect it. Many investigators have reported a similar result in human sub jects, that ENX markedly raised the plasma theophylline concentration and prolonged its T1 /2, whereas NFLX and OFLX had little or no effect on the pharmacokinetics of theophyl line (1)(2)(3)(4)(5)(6)(7)(8). Sekine et al (12) and Okazaki et al (26) have shown similar results in rats con cerning ENX and OFLX.…”

“…Since then, many investigators have demonstrated that ENX raises the plasma theophylline concentration and prolongs its elimination half-life (T1 /2). In contrast, other new quinolones, such as norfloxacin (NFLX) and ofloxacin (OFLX), have no or only a slight effect on the pharmacokinetics of theophyl line (2)(3)(4)(5)(6)(7)(8). It appears that the increase in the plasma theophylline concentration is due to a reduced metabolic clearance of theophylline in the liver induced by ENX, while NFLX and OFLX seem to have little effect on drug metabolizing activity in the liver.…”

“…Sekine et al (12) and Okazaki et al (26) have shown similar results in rats con cerning ENX and OFLX. Plasma protein binding and renal clearance of theophylline are reported to remain unchanged in patients treated with ENX or OFLX (1,2,5), so that the prolongation of the TI/2 of theophylline is considered to be due to reduced metabolic clearance in the liver. In rats, ENX and OFLX are also reported not to affect serum protein binding (26).…”

“…February 2,1990 Abstract-The effects of three new quinolones (enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX)) on acetaminophen-induced liver injury in rats were examined and compared with their effects on the elimination half-life (T1/2) of theophylline (in vivo) and on the 7-ethoxycoumarin (7-EC) O-deethylase activity in liver microsomes (in vitro).…”

The influence of quinolone derivatives on theophylline clearance.

“…Further investigation into this increase in plasma theophylline concentrations showed that neither theophylline protein binding nor theophylline renal clearance were influenced by the enoxacin co-medication; it was therefore concluded that the interaction mechanism might be a decreased theophylline metabolic clearance (Wijnands et al, 1985b).…”