Lack of pharmacokinetic interaction between moxifloxacin, a novel 8-methoxyfluoroquinolone, and theophylline.

OBJECTIVE

To investigate the plasma and urinary pharmacokinetics, safety and tolerability of theophylline and moxifloxacin after single and repeated doses of either compound administered alone or concomitantly with the other.

DESIGN

This was a randomised, multiple-dose, period-balanced, 3-way crossover study in healthy volunteers.

PARTICIPANTS

12 nonsmoking healthy volunteers, 21 to 30 years of age were included in this study.

METHODS

The investigational medications, all given orally, were as follows: treatment A, moxifloxacin 200mg alone; treatment B, theophylline 400mg alone; treatment C, theophylline 400mg plus moxifloxacin 200mg. Each drug or combination was given twice daily on days 2 to 4 of the 5-day study period and as single morning doses on days 1 and 5. The study periods were separated by 1-week washout intervals. The plasma and urinary pharmacokinetics of moxifloxacin and theophylline were characterised after the first (morning of day 1) and eighth (morning of day 5) doses.

RESULTS

At steady state, the plasma pharmacokinetics of theophylline for treatments B and C proved equivalent in terms of maximum concentration (Css(max)) and bodyweight- and dose-normalised Css(max) lestimated true ratio 96%, 90% confidence interval (CI) 87 to 105%] and also in terms of area under the concentration-time curve from 0 to 12 hours (AUCss(tau)) and normalised AUCss(tau) (ratio 95%, 90% CI 85 to 107%); the median times to Cmax(tmax) were also similar (5.0 and 6.0 hours for treatments B and C, respectively). The plasma pharmacokinetics of moxifloxacin for treatments A and C were equivalent with respect to Css(max) (estimated true ratio 109%, 90% CI 97 to 123%) and AUCss(tau) (ratio 104%, 90% CI 100 to 108%); the median tmax values were also similar (0.5 and 1.0 hour for treatments A and C, respectively). The treatments were well tolerated.

CONCLUSIONS

Moxifloxacin - in contrast to some older quinolones - does not interact pharmacokinetically with theophylline, confirming preclinical results on the absence of cytochrome P450-mediated metabolism.