“…Both have been shown to reduce blood flow, body temperature and blood pressure (Himmel, 2008;Kamendi et al, 2010;Cosmi et al, 2009;Delaunois et al, 2009), which is likely to have made the sampling more difficult. Indeed, no such problems were identified for theophylline-treated animals (a phosphodiesterase inhibitor known to stimulate increases in body temperature and blood pressure in rats, Delaunois et al, 2009). Therefore, for new test entities where these effects may not yet be known, these sampling difficulties may still be apparent and may add to variability in the pharmacokinetic data.…”