Phase I, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women.

This study evaluated the pulmonary disposition of eravacycline in 20 healthy adult volunteers receiving 1.0 mg of eravacycline/kg intravenously every 12 h for a total of seven doses over 4 days. Plasma samples were collected at 0, 1, 2, 4, 6, and 12 h on day 4, with each subject randomized to undergo a single bronchoalveolar lavage (BAL) at 2, 4, 6, or 12 h. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry, and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods. Penetration for ELF and AM was calculated by using a ratio of the area under the concentration time curve (AUC0-12) for each respective parameter against free drug AUC (fAUC0-12) in plasma. The total AUC0-12 in plasma was 4.56±0.94 µg·h/ml with a mean fAUC0-12 of 0.77±0.14 µg·h/ml. The eravacycline concentrations in ELF and AM at 2, 4, 6, and 12 h were means±the standard deviations (µg/ml) of 0.70±0.30, 0.57±0.20, 0.34±0.16, and 0.25±0.13 with a penetration ratio of 6.44 and 8.25±4.55, 5.15±1.25, 1.77±0.64, and 1.42±1.45 with a penetration ratio of 51.63, respectively. The eravacycline concentrations in the ELF and AM achieved greater levels than plasma by 6- and 50-fold, respectively, supporting further study of eravacycline for patients with respiratory infections.

Dietary quality assurance processes of the DASH-Sodium controlled diet study.

A thorough quality assurance (QA) program upholds the integrity of nutrition research studies by yielding reliable data and results. Continually evaluating the implementation of a procedure against a goal and making adjustments when needed enhance the quality of a study's conduct and outcomes. Controlled diet studies require QA processes at various steps beginning with the screening of study participants, through diet preparation and delivery to data collection. Staff training and observations with monitoring activities, are important so tasks are completed according to protocol. When several clinical sites participate as partners in a controlled diet study, uniform procedures must be followed and a formal standardized QA program will assist. The Dietary Approaches to Stop Hypertension (DASH)-Sodium study employed such a program, described in this article, that included training staff, observing procedures, monitoring data for completeness and accuracy, evaluating processes, giving feedback, and documenting that tasks were done according to protocol. Furthermore, QA processes were used in the areas of participant screening, orientation, diet adherence, food procurement and preparation, and exit interviews. Other researchers may implement similar activities to ensure quality in their nutrition research programs.