Influence of activated charcoal on the pharmacokinetics of moxifloxacin following intravenous and oral administration of a 400 mg single dose to healthy males.
OBJECTIVE
To evaluate the extent to which enterohepatic recycling circulation contributes to moxifloxacin bioavailability in healthy, males by administration of activated charcoal and to evaluate the efficacy of activated charcoal administration in decreasing systemic concentrations of moxifloxacin in the event of overdose.


METHODS
Nine healthy males, mean age 34 years (range 23-45 years) participated in a single centre, randomized, nonplacebo-controlled, three way crossover study. The pharmacokinetics of moxifloxacin in plasma and urine were determined for up to 96 h following a 400 mg single dose randomly administered on three separate occasions with a minimum washout phase of 1 week. Treatment A was 400 mg moxifloxacin IV as a 1 h infusion, treatment B was 400 mg moxifloxacin IV as a 1 h infusion with oral activated charcoal (5 g directly before the start of the infusion, 5 g immediately after the end of the infusion, and 10 g at 2, 4 and 8 h after the start of the infusion), treatment C was 400 mg oral moxifloxacin with activated charcoal (10 g 15 min before and at 2, 4 and 8 h after drug administration). The subjects underwent a series of clinical and laboratory tests.


RESULTS
Single 400 mg doses of moxifloxacin (PO and/or IV) were safe and well tolerated. The bioavailability of moxifloxacin was significantly decreased when given with charcoal (AUC = 35.5 (IV reference) vs 5.40 (PO) vs 28.5 (IV) mg l(-1) h). Concurrently peak concentrations were lowered C(max) = 3.38 (IV reference) vs 0.62(PO) vs 2.97 (IV) mg l(-1)) by approximately 85% (P < 0.05) following oral administration and by 20% after IV treatment (P < 0.05). Bioavailability amounted to 15.4% (95% confidence interval 9.6, 25.0%) for treatment B while it was 80.4% (95% confidence interval 76.3.6, 84.6%) for treatment C. Terminal half-lives were not affected. The kinetics of urinary excretion corroborated these findings.


CONCLUSIONS
The results of this study show that moxifloxacin undergoes pronounced enteric recycling after systemic uptake. In addition, these findings confirm that activated charcoal may be useful in treating moxifloxacin overdose by preventing its absorption.
Stass
H
H
BAYER AG, Pharma Research Centre, ICP, 42096 Wuppertal, Germany. Heino.Stass.hs@bayer-ag.de
Kubitza
D
D
Möller
J-G
JG
Delesen
H
H
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001372:Aza Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D002606:Charcoal / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D024841:Fluoroquinolones; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002606:Charcoal; D000077266:Moxifloxacin