Nonlinear distribution of atenolol between plasma and cerebrospinal fluid.

Long Evans rats were given atenolol doses ranging from 0.27 to 5.4 mg/kg by intraperitoneal injection Animals were dosed once every 2 hr for a total of five doses. Atenolol concentrations 1 hr after the last dose were measured from simultaneously obtained plasma and cerebrospinal fluid (CSF) samples CSF concentrations of atenolol were not proportional to plasma concentrations. The ratio of CSF/plasma concentrations was higher (0.33) at lower plasma atenolol levels (less than 100 ng/ml) than at the higher atenolol plasma levels (0.05) (P less than 0.001). The relationship between plasma and cerebrospinal fluid atenolol concentrations was best described by the sum of a Michaelis-Menten and linear function. Animals were also given atenolol doses and then subjected to global cerebral ischemia. The relationship of atenolol concentrations from plasma and CSF in these animals was linear, with a constant partition ratio of 0.02. Together these data show that atenolol partitioning between plasma and CSF is nonlinear and possibly an energy-dependent process.