RELATIONSHIP BETWEEN ENOXACIN AND CIPROFLOXACIN PLASMA-CONCENTRATIONSAND THEOPHYLLINE DISPOSITION

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.'