Source: Skeletal Radiol  |  Posted 9 years ago

Pharmacokinetic analysis provides a rationale for linezolid administration every 12 hours and suggests its effectiveness for the treatment of pulmonary infections.

Investigators from the Department of Epidemiology and Biostatistics and the Department of Medicine and the University of California, San Francisco in San Francisco, California, United States, determined the steady-state intrapulmonary concentrations and pharmacokinetic parameters of oral linezolid in 25 healthy adult male volunteers.

The subjects received 600 mg linezolid every 12 hours for a total of five doses. The patients were divided into five subgroups and each underwent bronchoscopy and bronchoalveolar lavage at four, eight, 12, 24, or 48 hours after administration of the last dose. Blood samples were collected prior to administration of the first and fifth dose and after bronchoscopy and bronchoalveolar lavage.

Results showed half-lives for linezolid in plasma, epithelial lining fluid and alveolar cells as 6.9, 7.0 and 5.7 hours, respectively. The percentage of time the drug stayed above the minimal inhibitory concentration (MIC) for the 12-hour dosing interval was 100 percent in both plasma and epithelial lining fluid.

The long half-lives and percentage of time spent above the MIC for both plasma and epithelial lining fluid suggest that 12-hour administrations are appropriate and that linezolid will be effective for pulmonary infections, the investigators conclude.