Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p>GSK1322322 is a potent peptide deformylase inhibitor with<jats:italic>in vitro</jats:italic>and<jats:italic>in vivo</jats:italic>activity against multidrug-resistant skin and respiratory pathogens. This report provides plasma and intrapulmonary pharmacokinetics, safety, and tolerability of GSK1322322 after repeat (twice daily intravenous dosing for 4 days) dosing at 1,500 mg. Plasma samples were collected over the last 12-hour dosing interval of repeat dosing following the day 4 morning dose (the last dose). Bronchoalveolar lavage samples were collected once in each subject, either before or at 2 or 6 h after the last intravenous dose. Plasma area under the concentration-time curve (AUC<jats:sub>0–τ</jats:sub>) was 66.7 μg · h/ml, and maximum concentration of drug in serum (C<jats:sub>max</jats:sub>) was 25.4 μg/ml following repeat doses of intravenous GSK1322322. The time course of epithelial lining fluid (ELF) and alveolar macrophages (AM) mirrored the plasma concentration-time profile. The AUC<jats:sub>0–τ</jats:sub>for ELF and AM were 78.9 μg · h/ml and 169 μg · h/ml, respectively. The AUC<jats:sub>0–τ</jats:sub>ratios of ELF and AM to total plasma were 1.2 and 2.5, respectively. These ratios increased to 3.5 and 7.4, respectively, when unbound plasma was considered. These results are supportive of GSK1322322 as a potential antimicrobial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered at<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</jats:ext-link>under registration number NCT01610388.)</jats:p>