Abstract
We investigated the effect of albumin (6%) on the (Β±)βisoprenalineβinduced relaxation of strips of isolated rat uterus and its antagonism by (β)βpropranoioi. The mean isoprenaline EC~50~ in the presence of albumin was significantly less than that in the absence of albumin (geometric mean 1.94 Β± 3.33 versus 3.21 Β± 3.50 nM, respectively; n = 14; p = 0.006, paired t test). This indicates enhancement of isoprenaline activity by albumin which could not be explained by protein binding, as this would have reduced activity. Geometric mean control K~B~ values for inhibition of isoprenaline by propranolol at 26.8 and 500 nM were 0.835 Β± 1.68(n = 10) and 0.889 Β± 1.60 nM (n = 34), respectively. In the presence of 6% albumin, K~B~ for propranolol was increased significantly to 13.3 Β± 1.8 nM (n = 27, p <0.001). Calculation of K~B~ in terms of the measured propranolol unbound concentration of 26.8 nM, after taking into account the lower isoprenaline EC~50~ in the presence of albumin, yielded a mean value of 0.725 Β± 1.86 nM, which was not significantly different from either control (p >0.05). Therefore, propranolol activity was as predicted by the unbound drug concentration in Contrast to isoprenaline activity. We conclude that albumin can alter in vitro drug activity by mechanisms in addition to the reduction of unbound drug concentration.