nach oben

Clinical Pharmacokinetics

Erschienen in:

01.12.2001 | Original Research Article

Effect of Probenecid on the Kinetics of a Single Oral 400mg Dose of Moxifloxacin in Healthy Male Volunteers

verfasst von: Dr Heino Stass, Richard Sachse

Erschienen in: Clinical Pharmacokinetics | Sonderheft 1/2001

Einloggen, um Zugang zu erhalten

Abstract

Objective

To investigate the effect of oral probenecid on the pharmacokinetics of oral moxifloxacin in healthy adult male volunteers.

Design and setting

This was a nonblinded, randomised, 2-way crossover study.

Patients and participants

12 male Caucasian volunteers (mean age 33.7 years) participated in the study.

Methods

A single oral dose of moxifloxacin 400mg was administered after an overnight fast with or without a 2-day course of probenecid 500mg twice daily starting at 1 hour before the moxifloxacin dose. There was a washout phase of at least 1 week between the 2 treatments. Samples of plasma and urine were taken according to predefined sampling schedules and the concentrations of moxifloxacin were determined with a validated high performance liquid chromatography assay with fluorescence detection. Noncompartmental pharmacokinetic data were calculated.

Results

Pharmacokinetic results with and without probenecid were virtually identical except for a slight delay in absorption with probenecid, indicated by a very slightly increased time to maximum concentration and a decreased maximum concentration (approximately 10%), which was not clinically relevant. Probenecid had no significant influence on the renal elimination of moxifloxacin, suggesting urinary excretion by glomerular filtration and partial tubular reabsorption. Safety and tolerability were good, with no clinically relevant drug-related adverse events or changes in laboratory parameters.

Conclusion

Dosage adjustments for moxifloxacin are not necessary when it is administered together with probenecid.

Balfour JAB, Wiseman LR. Moxifloxacin. Drags 1999; 57: 365–73

MacGowan AP. Moxifloxacin (BAY 12-8039): a new methoxy quinolone antibacterial. Exp Opin Invest Drugs 1999; 8: 181–99CrossRef

Wise R. Areview of the clinical pharmacology of moxifloxacin, a new 8-methoxyquinolone, and its potential relation to therapeutic efficacy. Clin Drug Invest 1999; 17: 365–87CrossRef

Stass H, Dalhoff A, Kubitza D, et al. Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxyquinolone, administered to healthy subjects. Antimicrob Agents Chemother 1998; 42(8): 2060–5CrossRef

Stass HH, Kubitza D. Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. J Antimicrob Chemother 1999; 43 Suppl. B: 83–9CrossRef

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

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

Stass H, Kubitza D, Schwietert HR, et al. BAY 12-8039 does not interact with theophylline [abstract no. 3356 ]. 20th International Congress on Chemotherapy; 1997 Jun 29–Jul 3; Sydney, Australia: 108

Stass HH, Müller F, Hundt HKL, et al. Study of the influence of once-daily dosing of 400 mg moxifloxacin on pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers [abstract no. A13]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 25–27; San Diego, California: 4

10.

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

11.

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

12.

Siefert HM, Domdey-Bette A, Henninger K, et al. Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: a comparison in humans and other mammalian species. J Antimicrob Chemother 1999; 43 Suppl B: 69–76CrossRef

13.

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

14.

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

15.

Beyer KH, Russo HF, Tillson EK, et al. Benemid, p-(di-n-propylsulfamyl)-benzoic acid: its renal affinity and its elimination. Am J Physiol 1951; 166: 625–40CrossRef

16.

Drummer OH, Thompson J, Hooper R, et al. Effect of probenecid on the disposition of Captopril and Captopril dimer in the rat. Biochem Pharmacol 1985; 34: 3347–51CrossRef

17.

Bax RP, Bastain W, Featherstone A, et al. The pharmacokinetics of meropenem in volunteers. J Antimicrob Chemother 1989; 24 Suppl. A: 311–20CrossRef

18.

Chatton JY, Odone M, Besseghir K, et al. Renal secretion of 3′-azido-3′-deoxythymidine by the rat. J Pharmacol Exp Ther 1990; 255: 140–5PubMed

19.

Nadai M, Apichartpichean R, Hasegawa T, et al. Pharmacokinetics and the effect of probenecid on the renal excretion mechanism of diprophylline. J Pharm Sci 1992; 81: 1024–7CrossRef

20.

Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet 1997; 32: 101–19CrossRef

21.

Foote EF, Halstenson CE. Effects of probenecid and Cimetidine on renal disposition of Ofloxacin in rats. Antimicrob Agents Chemother 1998; 42: 456–8PubMedPubMedCentral

22.

Jaehde U, Sörgel F, Reiter A, et al. Effect of probenecid on the distribution and elimination of Ciprofloxacin in humans. Clin Pharmacol Ther 1995; 58: 532–41CrossRef

23.

Nakashima M, Uematsu T, Kosuge K, et al. Single- and multiple-dose pharmacokinetics of AM-1155, a new 6-fluoro-8-methoxy quinolone, in humans. Antimicrob Agents Chemother 1995; 39: 2635–40CrossRef

24.

Steinijans VW, Hartmann M, Huber R, et al. Lack of pharmacokinetic interaction as an equivalence problem. Int J Clin Pharm Ther Tox 1991; 29(8): 323–8

25.

Stass HH, Halabi A, Delesen H. No dose adjustment is needed for patients with renal impairment receiving oral moxifloxacin [abstract A14]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 25–27; San Diego, California: 5

Titel: Effect of Probenecid on the Kinetics of a Single Oral 400mg Dose of Moxifloxacin in Healthy Male Volunteers
verfasst von: Dr Heino Stass
Richard Sachse
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/10.2165/00003088-200140001-00010

Springer Medizin

Abstract

Objective

Design and setting

Patients and participants

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Sonderheft 1/2001

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

Effects of Iron Supplements on the Oral Bioavailability of Moxifloxacin, a Novel 8-Methoxyfluoroquinolone, in Humans

Pharmacokinetics, Safety and Tolerability of Moxifloxacin, a Novel 8-Methoxyfluoroquinolone, after Repeated Oral Administration

The Influence of Age and Gender on the Pharmacokinetics of Moxifloxacin

Lack of Pharmacokinetic Interaction between Moxifloxacin, a Novel 8-Methoxyfluoroquinolone, and Theophylline

Evaluation of the Influence of Antacids and H2 Antagonists on the Absorption of Moxifloxacin after Oral Administration of a 400mg Dose to Healthy Volunteers