Influence of activated charcoal on the pharmacokinetics of moxifloxacin following intravenous and oral administration of a 400 mg single dose to healthy males

Abstract

Br J Clin Pharmacol AimsTo 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. MethodsNine 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. ResultsSingle 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. ConclusionsThe 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. Moxifloxacin charcoal interactionBr J Clin Pharmacol 59 :5 537

Application of Physiologically‐Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin

“…(as 60‐minute infusion) or p.o. administration of 400 mg moxifloxacin: The minimum and maximum that were observed in adults were 11.8 and 71.7 mg·hour/L for AUC (0–24 h) and 1.5 and 6.9 mg/L for C max , with more than 95% between 20–60 mg · hour/L and 2–6.5 mg/L, respectively …”

Investigating the Enteroenteric Recirculation of Apixaban, a Factor Xa Inhibitor: Administration of Activated Charcoal to Bile Duct-Cannulated Rats and Dogs Receiving an Intravenous Dose and Use of Drug Transporter Knockout Rats

“…Therefore, AC removes apixaban from the body by preventing its reabsorption. AC has been shown to block EHR of some drugs in human and animal studies (Gadgil et al, 1982;Heimer and Englund, 1986;Roberts et al, 2002;Stass et al, 2005). Additionally, the shorter half-life and lower exposures of moxifloxacin and phenobarbital upon administration of AC in humans and rabbits following i.v.…”

“…Additionally, the shorter half-life and lower exposures of moxifloxacin and phenobarbital upon administration of AC in humans and rabbits following i.v. drug administration has been ascribed to AC blocking enteroenteric recycling of the drugs (Wakabayashi et al, 1994;Stass et al, 2005).…”

Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide

“…The use of activated charcoal as bile-binding agent for the purpose of impeding enterohepatic recycling of xenobiotics is already well established (Chyka et al, 2005;Stass et al, 2005;Taft, 2009). Also, PK studies of interaction between drugs and activated charcoal have been used previously for determining if the active ingredient or related molecules undergo extensive recycling; reduced exposure coupled with accelerated elimination of the investigated molecule in the charcoal study arm are classic indicators of discontinuing/minimizing the recycling process (Sörgel et al, 1989;Elomaa et al, 2001;Wang et al, 2014).…”