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Antimicrobial Agents and Chemotherapy, June 2001, p. 1843-1846, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1843-1846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pharmacokinetics and Tissue Penetration of Linezolid following Multiple Oral Doses

Thekli Gee, Richard Ellis,dagger Gillian Marshall, Jenny Andrews, Janet Ashby, and Richard Wise*

Department of Microbiology, City Hospital NHS Trust, Birmingham, B18 7QH, United Kingdom

Received 7 August 2000/Returned for modification 17 December 2000/Accepted 26 March 2001

The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 µg/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 µg/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) µg · h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.

* Corresponding author. Mailing address: Department of Microbiology, City Hospital NHS Trust, Birmingham, B18 7QH, United Kingdom. Phone: 121 507 4255. Fax: 121 551 7763. E-mail: r.wise{at}bham.ac.uk.

dagger Present address: Department of Microbiology, Tyneside District Hospital, South Shields, Tyne and Wear, NE34 0PL, England.

Antimicrobial Agents and Chemotherapy, June 2001, p. 1843-1846, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1843-1846.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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