A Change in Posture Significantly Affects Plasma Concentrations of Large Molecules Such as IgG Antibodies

In several studies with monoclonal antibodies, we observed spikes in plasma concentration profiles coinciding with a change of posture of study subjects. We hypothesized that these unexpected changes were due to fluid shifts from plasma to the interstitium. The objective of this study was to investigate size and time course of the change in total immunoglobulin G (IgG) concentration after a change in posture. Thirty-two healthy subjects were enrolled. After entry in the clinic, subjects remained upright for at least 1 hour, followed by IgG sampling. Thereafter, subjects remained supine or seated (16 subjects each) for 60 minutes while IgG was sampled frequently. The within-subject day-to-day variability of IgG measured in the same position was only 2.6%. After a change in posture from standing to supine, IgG dropped rapidly in all subjects during the first 10 minutes in the supine position (9.0% decrease) and more slowly thereafter, up to a 12.3% decrease after 60 minutes. After a change in posture from standing to sitting, the decrease in IgG was more variable and modest. After 10 minutes of sitting, IgG was 3.6% lower, and after 60 minutes IgG was 7.8% lower. Changing posture causes a bias of more than 10% in plasma concentrations of total IgG. Most of the change is reached after being 15 minutes in the same position. In clinical trials in which plasma concentrations of high-molecular drugs, highly protein-bound drugs, endogenous proteins, or blood cells are assessed, standardizing posture per time point is a useful approach for reducing variability.