Jd. Davis et al., RELATIONSHIP BETWEEN ENOXACIN AND CIPROFLOXACIN PLASMA-CONCENTRATIONSAND THEOPHYLLINE DISPOSITION, Pharmaceutical research, 11(10), 1994, pp. 1424-1428
Certain fluoroquinolone antibiotics affect theophylline (THEO) disposi
tion by inhibition of its metabolism, yet no studies to date have inve
stigated the relationship between fluoroquinolone plasma concentration
and THEO pharmacokinetics, The effects of two fluoroquinolones, enoxa
cin (ENOX) and ciprofloxacin (CIPRO), have been studied in male Spragu
e-Dawley rats (n = 33-46) at steady state plasma concentrations of 0-3
3 mg.l(-1), achieved by supplementing an intravenous bolus dose with a
constant rate infusion. The effects of steady state ENOX and CIPRO pl
asma concentrations on the clearance of THEO determined after an intra
venous bolus dose of 6 mg.kg(-1) were described using a competitive in
hibition model. The model consisted of two components, one describing
a residual component of THEO clearance, which was unaffected by fluoro
quinolone, the other describing the non-linear reduction of THEO clear
ance by fluoroquinolone. The residual clearance estimated from the mod
el was comparable to renal clearance for THEO in the rat. The potency
of each fluoroquinolone was characterised by a Ki value, the concentra
tion reducing THEO clearance by 50% of the maximum change. These value
s were 4.7 mu M and 16.3 mu M for ENOX and CIPRO, respectively. Thus,
in this study, ENOX was found to be a more potent inhibitor of THEO cl
earance than CIPRO. The method allowed direct in vivo comparison of po
tency between different fluoroquinolones, as pharmacokinetic differenc
es, such as clearance, volume of distribution and bioavailability, wer
e 'designed out.'