Pharmacokinetic assessments
Since literature suggests a diurnal variation in LPS-induced TNFα release [21], timing of blood sampling was strictly controlled in our study. Clock times for drug administration were standardized within and between study cohorts. Org 48775-0 serum concentrations were determined by at Schering-Plough using a liquid-chromatographic assay with mass spectrometric detection (LC-MS) after solid phase extraction, using a lower limit of quantitation (LLOQ) of 0.0250 ng/mL. Pharmacokinetic parameters of Org 48775-0 were determined based on the individual plasma concentration-time data and included peak plasma concentration (Cmax), time to reach peak plasma concentration (tmax), area under the plasma concentration-time curve extrapolated to infinity (AUC), elimination half-life (t½), and apparent clearance (CL/F).