Influence of the blood-brain pH gradient on brain phenobarbital uptake during status epilepticus

Brain uptake and blood concentrations of phenobarbital were determined in rats during pentylenetetrazol-induced status epilepticus and compared to nonconvulsing controls. Brain phenobarbital concentrations and the brain-to-blood phenobarbital ratio were increased 2-fold in freely convulsing animals as compared to controls. The degree of systemic acidosis during motor convulsions was greater than the degree of brain acidosis. Because phenobarbital is a weak acid, this pH gradient favors movement of phenobarbital into the brain during status epilepticus. Motor paralysis prevented the development of systemic acidosis and the brain-blood partition of phenobarbital was similar to that of nonconvulsing controls. Blood phenobarbital concentrations were slightly higher in animals paralyzed during status as compared to controls, presumably due to hemodynamic effects of convulsions. These studies, as well as our previous studies with lidocaine, support the idea that the brain-blood pH gradient is an important determinant of drug uptake by the brain during seizures.