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).