JAC Advance Access originally published online on September 20, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Antimicrobial Chemotherapy (2002) 50, 707-712
© 2002 The British Society for Antimicrobial Chemotherapy
Single- and multiple-dose pharmacokinetics of linezolid and co-amoxiclav in healthy human volunteers
1 Department of Chest and Infectious Diseases, Chest Hospital Heckeshorn, affil. Freie Universität Berlin, Zum Heckeshorn 33, D-14109 Berlin; 2 Institute of Clinical Chemistry and Pathobiochemistry and 3 Department of Medical Physics, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany; 4 Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden
Received 16 January 2002; returned 15 April 2002; revised 30 May 2002; accepted 24 June 2002
In an open, randomized, two-period crossover study the pharmacokinetics of linezolid and co-amoxiclav were investigated after single- and multiple-dose administration in 12 healthy volunteers (six females and six males). Linezolid was given in tablets of 600 mg twice a day for 7 days and co-amoxiclav in tablets of 1000 mg (875 + 125 mg) once a day for 7 days. The wash-out period was 4 weeks between the administration of the two antibacterial agents. Blood and urine samples were collected on days 1 and 7 before and at different time points up to 24 h after medication. The concentrations of the antibiotics in serum and urine were measured by validated high-performance liquid chromatography methods. Linezolid exhibited a mean Cmax of 14.5 ± 4.6 mg/L after Tmax of 47.5 ± 20.1 min on day 1, with a significant increase to 24.0 ± 6.9 mg/L on day 7 (P < 0.01). The AUDtot (total area under the data) revealed a significant increase from 140.5 ± 28.3 mg·h/L on day 1 to 220.2 ± 42.6 mg·h/L on day 7 (P < 0.01). There were no significant differences in terminal elimination half-life between days 1 and 7 (9.53 ± 2.87 versus 7.97 ± 3.08 h) or in total clearance (71.6 ± 17.6 versus 81.5 ± 14.7 ml/min·1.73 m2). Results are in agreement with the assumption of a limited accumulation of linezolid under the dosage regimen given. Serum linezolid concentrations in females were always higher than those in males. The volume of distribution Vss/f differed significantly between females and males (41.6 ± 4.2 versus 52.2 ± 3.3 L/70 kg; P < 0.01). Pharmacokinetic parameters of amoxicillin and clavulanic acid found in this study were similar to previously published data. No accumulation was found with co-amoxiclav. No serious adverse event was observed with the study drugs.
Keywords: linezolid, co-amoxiclav, pharmacokinetics, multiple dosing
* Corresponding author. Tel: +49-30-8002-2223; Fax: +49-30-8002-2623; E-mail: haloheck{at}zedat.fu-berlin.de
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Schmidt, R. Banks, V. Kumar, K. H. Rand, and H. Derendorf Clinical Microdialysis in Skin and Soft Tissues: An Update J. Clin. Pharmacol., March 1, 2008; 48(3): 351 - 364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Moreillon, W. R. Wilson, R. Leclercq, and J. M. Entenza Single-Dose Oral Amoxicillin or Linezolid for Prophylaxis of Experimental Endocarditis Due to Vancomycin-Susceptible and Vancomycin-Resistant Enterococcus faecalis Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1661 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Alou, M. J. Gimenez, D. Sevillano, L. Aguilar, N. Gonzalez, O. Echeverria, M. Torrico, P. Coronel, and J. Prieto Are {beta}-lactam breakpoints adequate to define non-susceptibility for all Haemophilus influenzae resistance phenotypes from a pharmacodynamic point of view? J. Antimicrob. Chemother., April 1, 2007; 59(4): 652 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Buerger, N. Plock, P. Dehghanyar, C. Joukhadar, and C. Kloft Pharmacokinetics of unbound linezolid in plasma and tissue interstitium of critically ill patients after multiple dosing using microdialysis. Antimicrob. Agents Chemother., July 1, 2006; 50(7): 2455 - 2463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Grunder, Y. Zysset-Aschmann, F. Vollenweider, T. Maier, S. Krahenbuhl, and J. Drewe Lack of Pharmacokinetic Interaction between Linezolid and Antacid in Healthy Volunteers Antimicrob. Agents Chemother., January 1, 2006; 50(1): 68 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Dehghanyar, C. Burger, M. Zeitlinger, F. Islinger, F. Kovar, M. Muller, C. Kloft, and C. Joukhadar Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses Antimicrob. Agents Chemother., June 1, 2005; 49(6): 2367 - 2371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E Stein, S. L Schooley, C. A Peloquin, V. Kak, D. H Havlichek, D. M Citron, K. L Tyrrell, and E. J. Goldstein Pharmacokinetics and Pharmacodynamics of Linezolid in Obese Patients with Cellulitis Ann. Pharmacother., March 1, 2005; 39(3): 427 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Humphrey, M. H. Shattuck, R. J. Zielinski, M.-S. T. Kuo, J. J. Biermacher, D. P. Smith, J. L. Jensen, R. D. Schaadt, G. E. Zurenko, and I. M. Richards Pharmacokinetics and Efficacy of Linezolid in a Gerbil Model of Streptococcus pneumoniae-Induced Acute Otitis Media Antimicrob. Agents Chemother., April 1, 2003; 47(4): 1355 - 1363. [Abstract] [Full Text] [PDF]
|
|