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.


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


METHODS
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.
Stass
H
H
Pharma Research Centre, Institute of Clinical Pharmacology, Bayer AG, Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Kubitza
D
D
D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D001372:Aza Compounds; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004334:Drug Administration Schedule; D004347:Drug Interactions; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D016014:Linear Models; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D000077266:Moxifloxacin; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000494:pharmacology*; D011804:Quinolines; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*
D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D010726:Phosphodiesterase Inhibitors; D011804:Quinolines; D013806:Theophylline; D019363:Cytochrome P-450 CYP1A1; D000077266:Moxifloxacin