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Effects of Enterai Feeding on the Oral Bioavailability of Moxifloxacin in Healthy Volunteers

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Abstract

Background and objective: Moxifloxacin is a new generation fluoroquinolone antimicrobial agent used worldwide. In clinical practice in intensive care units, moxifloxacin may be frequently administered through a nasogastric feeding tube. In the absence of an oral liquid formulation and since the multivalent cations contained in enterai feeds may potentially impair absorption of moxifloxacin administered via this route, we studied the effect of concomitant enterai feeding on the pharmacokinetics and tolerability of moxifloxacin administered as a crushed tablet through the nasogastric tube.

Participants and methods: This was a single-centre, open-label, randomised, controlled, nonblinded, three-way crossover study. Twelve young healthy volunteers (nine females and three males) aged 20–42 years were included in the study. Each participant received three separate treatment regimens in a randomised fashion: an intact moxifloxacin 400mg tablet (regimen A, reference treatment), a crushed moxifloxacin 400mg tablet as a suspension through a nasogastric tube with water (regimen B) and a crushed moxifloxacin 400mg tablet as a suspension through a nasogastric tube with enterai feeding (regimen C). A washout period of 1-week followed each treatment. Concentrations of moxifloxacin in serum were measured by a validated high-performance liquid chromatography method. Pharmacokinetic parameters were calculated by noncompartmental methods. Additionally, the primary parameters indicative for changes in absorption (area under the serum concentration-time curve from time zero to infinity [AUC∞] and peak serum concentration [Cmax]), were tested for bioequivalence, assuming log-normally distributed data using ANOVA.

Results: All moxifloxacin treatment regimens were well tolerated. The AUC∞ was slightly, but not statistically significantly, decreased in treatments with regimens B and C. AUC∞ (geometric means 39.6 [regimen A] vs 36.1 [regimen B] vs 36.1 mg · h/L [regimen C] and point estimates 91% for B: A and C: A) indicated bioequivalence of the treatments. Bioequivalence criteria of AUC∞ and Cmax were met upon retrospective statistical analysis. Likewise Cmax after moxifloxacin administration through nasogastric tube with water (regimen B) and with tube feed (regimen C) were slightly decreased (geometric means 3.20 [regimen A] vs 3.05 [regimen B] vs 2.83 mg/L [regimen C]; point estimates 88% for B: A, and 95% for C: A). They were within the range seen in other studies conducted with oral administration of the drug. No statistically significant differences were observed in time to reach Cmax (tmax; median 1.75 [regimen A] vs 1.00 [regimen B] vs 1.75 hours [regimen C]). Thus, the rate of absorption of moxifloxacin was not affected by administration through a nasogastric tube. This route of ingestion seems to be associated with a slight loss of bioavailability independent of the carrier medium used (water vs enterai feed); no clinically relevant interaction with the multivalent cations contained in the enterai feed was observed, indicating that moxifloxacin and enterai nutrition can be administered concomitantly.

Conclusion: There was no clinically relevant effect of enterai feeding on the pharmacokinetics of oral moxifloxacin in healthy volunteers. This result has to be evaluated in patients, particularly those from the intensive care unit, who are characterised by severe infectious and/or concomitant diseases that might influence absorption of moxifloxacin.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

The expert technical assistance of Peter-Michael Hopfe and Beate Schoening is gratefully acknowledged. This investigation was supported by a grant from Bayer HealthCare AG, Wuppertal, Germany. Drs Stass and Thuss are employees of Bayer HealthCare AG, Wuppertal, Germany.

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Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, University Otto-von Guericke, Magdeburg, Germany

    Olaf Burkhardt & Tobias Weite

  2. Department of Pulmonary Medicine, Medical School Hannover, Hannover, Germany

    Olaf Burkhardt & Tobias Weite

  3. Department of Pharmaceutics, College of Pharmacy, University of Florida, PO Box 100494, Gainesville, Florida, 32610, USA

    Olaf Burkhardt

  4. Pharma Research Centre, Institute of Clinical Pharmacology, Bayer HealthCare AG, Wuppertal, Germany

    Heino Stass & Uwe Thuss

  5. Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany

    Klaus Borner

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  1. Olaf Burkhardt
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  2. Heino Stass
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  3. Uwe Thuss
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  4. Klaus Borner
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  5. Tobias Weite
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Correspondence to Olaf Burkhardt.

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Burkhardt, O., Stass, H., Thuss, U. et al. Effects of Enterai Feeding on the Oral Bioavailability of Moxifloxacin in Healthy Volunteers. Clin Pharmacokinet 44, 969–976 (2005). https://doi.org/10.2165/00003088-200544090-00006

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