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Clinical Pharmacokinetics

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01.12.2001 | Original Research Article

Effects of Sucralfate on the Oral Bioavailability of Moxifloxacin, a Novel 8-Methoxyfluoroquinolone, in Healthy Volunteers

verfasst von: Dr Heino Stass, Uwe Schühly, Jan-Georg Möller, Heinz Delesen

Erschienen in: Clinical Pharmacokinetics | Sonderheft 1/2001

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Abstract

Objective

To investigate the effect of concomitant Al³⁺ (sucralfate) administration on the pharmacokinetics and tolerability of moxifloxacin.

Design

This was a single-centre, randomised, nonblinded, 2-way crossover study in healthy volunteers.

Participants

12 healthy men (age 21 to 41 years) were enrolled in the study.

Methods

The plasma and urinary pharmacokinetics of moxifloxacin were characterised up to 72 hours after single doses of moxifloxacin 400mg administered orally either alone or together with 190mg of Al³⁺ (Sucralfat-Ratiopharm® 1000) given immediately before and at 5, 10, 15 and 24 hours after the dose of moxifloxacin. There was a 2-week washout phase between the treatments.

Results

The treatments were well tolerated. The concomitant administration of Al³⁺ reduced the bioavailability of moxifloxacin [geometric mean area under the concentration-time curve from zero to infinity (AUC∞) 12.9 versus 32.2 mg/L · h; relative bioavailability 40%, 90% confidence interval (CI) 33 to 49%] and slowed down the absorption rate [median time to maximum concentration (tmax) 3.5 versus 1.0 hours], with a reduction of the maximum plasma concentration (Cmax) [geometric mean C_max0.82 versus 2.83 mg/L; estimated true ratio of C_max 29%, 90% CI 20 to 42%].

Conclusions

Concomitant ingestion with sucralfate and/or oral Al³⁺-containing antacids significantly reduces the bioavailability of moxifloxacin. This is compatible with reduced solubilisation as a consequence of a chelation reaction with polyvalent cations, a common finding for quinolones. Therefore, staggered administration of moxifloxacin and Al³⁺-containing or related cationic interactants should be considered to avoid a loss of therapeutic efficacy due to subtherapeutic plasma concentrations of the quinolone.

Dalhoff A, Petersen U, Endennann R. In vitro activity of BAY 12-8039, a new 8-methoxyquinolone. Chemotherapy 1996; 42: 410–25CrossRef

Blondeau JM, Felmingham D. In vitro and in vivo activity of moxifloxacin against community respiratory tract pathogens. Clin Drug Invest 1999; 18: 57–78CrossRef

Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995; 12: 314–33CrossRef

Deppermann KM, Lode H. Fluoroquinolones: interaction profile during enterai absorption. Drugs 1993; 45 Suppl. 3: 65–72CrossRef

Lomaestro BM, Bailie GR. Quinolone-cation interactions: a review. DICP 1991; 25: 1249–58CrossRef

Stass H, Kubitza D. Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J Antimicrob Chemother 1999; 43 Suppl. B: 83–90CrossRef

Ballow C, Lettieri J, Agarwal V, et al. Absolute bioavailability of moxifloxacin. Clin Ther 1999; 21: 513–22CrossRef

Stass H, Kubitza D, Unger S. The effect of food on the oral bioavailability of moxifloxacin in healthy male volunteers. Moxifloxacin in Practice 2000; 3: 15–23

Stass H, Kubitza D. Effects of dairy products on the oral bioavailability of moxifloxacin, a novel 8-methoxyfluoroquinolone, in healthy volunteers. Clin Pharmacokinet 2001; 40 Suppl. 1: 33–38CrossRef

10.

Stass H, Böttcher M, Ochmann K. Evaluation of the influence of antacids and H₂ antagonists on the absorption of moxifloxacin after oral administration of a 400mg dose to healthy volunteers. Clin Pharmacokinet 2001; 40 Suppl. 1: 39–48CrossRef

11.

Stass H, Wandel C, Delesen H, et al. Effect of calcium supplements on the oral bioavailability of moxifloxacin in healthy male volunteers. Clin Pharmacokinet 2001; 40 Suppl. 1: 27–32CrossRef

12.

Garey KW, Amsden GW. Trovafloxacin: an overview. Pharmacotherapy 1999; 19: 21–34CrossRef

13.

Lee LJ, Hafkin B, Lee ID, et al. Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects. Antimicrob Agents Chemother 1997; 41: 2196–200CrossRef

14.

Zix JA, Geerdes-Fenge HF, Rau M, et al. Phamiacokinetics of Sparfloxacin and interaction with cisapride and sucralfate. Antimicrob Agents Chemother 1997; 41: 1668–72CrossRef

15.

Spivey JM, Cummings DM, Pierson NR. Failure of Prostatitis treatment secondary to probable Ciprofloxacin-sucralfate drug interaction. Pharmacotherapy 1996; 16: 314–6PubMed

16.

Lehto P, Kivisto KT. Different effects of products containing metal ions on the absorption of lomefloxacin. Clin Pharmacol Ther 1994; 56: 477–82CrossRef

17.

Lehto P, Kivisto KT. Effect of sucralfate on absorption of norfloxacin and Ofloxacin. Antimicrob Agents Chemother 1994; 38: 248–51CrossRef

18.

Kawakami J, Matsuse T, Kotaki H, et al. The effect of food on the interaction of Ofloxacin with sucralfate in healthy volunteers. Eur J Clin Pharmacol 1994; 47: 67–9CrossRef

19.

Marchbanks CR. Drug-drug interactions with fluoroquinolones. Pharmacotherapy 1993; 13(2 Pt 2): 23S–8PubMed

20.

Stass H, Dalhoff A. Determination of BAY 12-8039, a new 8-methoxy-quinolone, in human body fluids by highperformance liquid chromatography with fluorescence detection using on column focusing; J Chromatogr B Biomed Sci Appl 1997; 702: 163–74CrossRef

21.

Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Marcel Dekker Inc., 1982

22.

Grasela Jr TH, Schentag JJ, Sedman AJ, et al. Inhibition of enoxacin absorption by antacids or ranitidine. Antimicrob Agents Chemother 1989; 33: 615–7CrossRef

23.

Stass H, Ochmann K. Study to evaluate the interaction between BAY 12-8039 and ranitidine [abstract no. 3357]. 20th International Congress on Chemotherapy; 1997 Jun 29–Jul 3; Sydney, Australia: 108

24.

Stass H, Kubitza D. Effects of iron supplements on the oral bioavailability of moxifloxacin, a novel 8-methoxyfluoroquinolone, in humans. Clin Pharmacokinet 2001; 40 Suppl. 1: 57–62CrossRef

25.

Stass H, Böttcher M, Horstmann R. Study to evaluate the interaction between BAY 12-8039 and antacids [abstract no. 3358). 20th International Congress on Chemotherapy; 1997 Jun 29–Jul 3; Sydney, Australia: 108

26.

Davies B, Maesen FPV. Drug interactions with quinolones. Rev Infect Dis 1989; 11 Suppl. 5: 1083–90CrossRef

27.

Janknegt R. Drug interactions with quinolones. J Antimicrob Chemother 1990; 26 Suppl. D: 7–29CrossRef

28.

Knupp CA, Barbhaiya RH. A multiple-dose pharmacokinetic interaction study between didanosine (Videx) and Ciprofloxacin (Cipro) in male subjects seropositive for HIV but asymptomatic. Biopharm Drug Dispos 1997; 18: 65–77CrossRef

Titel: Effects of Sucralfate on the Oral Bioavailability of Moxifloxacin, a Novel 8-Methoxyfluoroquinolone, in Healthy Volunteers
verfasst von: Dr Heino Stass
Uwe Schühly
Jan-Georg Möller
Heinz Delesen
Publikationsdatum: 01.12.2001
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe Sonderheft 1/2001
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200140001-00007

Springer Medizin

Abstract

Objective

Design

Participants

Methods

Results

Conclusions

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