Predicting the ciprofloxacin‐theophylline interaction from single plasma theophylline measurements.

Abstract

The effect of ciprofloxacin treatment on theophylline clearance was evaluated with a theophylline multiple dose, multiple sample protocol and with a single dose, single sample protocol. The object was to determine whether a single dose, single sample protocol for estimating theophylline clearance could be used as a screening strategy for evaluating host factor influences on theophylline clearance. Ciprofloxacin (750 mg per os) was administered every 12 h for nine doses in the multidose study and every 12 h for seven doses in the single dose protocol. Subjects were sixteen healthy, non‐smoking young adult males. The oral clearance of theophylline at steady state, (CL/F)ss, decreased from a mean (+/‐ s.d.) value of 0.035 (+/‐ 0.008) 1 h‐1 kg‐1 to 0.024 (+/‐ 0.004) 1 h‐1 kg‐1 during ciprofloxacin treatment. Single sample estimates of theophylline clearance, CL/F, similarly decreased from 0.040 (+/‐ 0.014) 1 h‐1 kg‐1 to 0.018 (+/‐ 0.008) 1 h‐1 kg‐1. Mean theophylline clearances were significantly different when comparing control with ciprofloxacin treatment means (P less than 0.01), but were not different when comparing single sample vs multiple sample clearances for a given treatment (i.e. control or ciprofloxacin). It is concluded that a single dose, single sample strategy may be used in screening for host‐factor influences on theophylline clearance.

In vivo Evidence that Theophylline Is Metabolized Principally by CYP1A in Rats

“…We have described the suitability of the ophylline as a single-sample probe of hepatic mixed function oxidase on the basis of its pharmacokinetics [12] and have demon strated the fidelity with which such single sample CL estimates can qualitatively and quantitatively predict the influence of host factors on theophylline CL when compared to more classical multisample-based CL esti mates [13]. In the present investigation, our objective was to evaluate the selectivity of theophylline metabolism in rats as a prelimi nary means of determining whether it is likely to be a useful selective in vivo single-sample probe of cytochrome P-450 activity in hu mans as well.…”

Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline.

“…The ability of fluoroquinolones to inhibit theophylline clearance is well documented. The magnitude of the lowering in clearance varies between the fluoroquinolones with a 64% decrease in theophylline clearance by enoxacin (Rogge et al, 1988;Wijnands et al, 1986), and a 30% decrease with ciprofloxacin or pefloxacin (Bachmann et al, 1988;Wijnands et al, 1986). Theophylline is metabolised by three major pathways, 1-demethylation, 3-demethylation and 8-hydroxylation (Birkett et al, 1985) and the effects of the fluoroquinolones on each of these metabolic pathways has not been established.…”

Co‐administration of ciprofloxacin and cyclosporin: lack of evidence for a pharmacokinetic interaction.

“…Ciprofloxacin is a broad spectrum fluoroquinolone antibiotic which is widely known to increase theophylline blood concentrations in patients (Raoof et al, 1986;Bachmann et al, 1988). Inhibition of cytochrome P-450 mediated theophylline metabolism by ciprofloxacin or its 4-oxo metabolite has been implicated as a possible mechanism of the interaction (Wijnands et al, 1986).…”