Brain phenobarbital uptake during prolonged status epilepticus.
The brain uptake of phenobarbital during prolonged status epilepticus (3 h) was studied in paralyzed, ventilated sheep. The first 30 min of status epilepticus was characterized by systemic hypertension, increased CBF, increased peripheral vascular resistance, a fall in brain pH, and an elevation in brain lactate concentrations. Subsequently, hemodynamic factors normalized and brain acidosis persisted. Phenobarbital administered during the early phase of status epilepticus produced higher levels of brain phenobarbital concentration, which was greatest at the earliest sample time (5 min following infusion), compared to nonseizure controls. This elevation persisted for the first 3 h following the infusion. Phenobarbital administration during the established phase of status epilepticus, when systemic blood pressure, peripheral vascular resistance, and CBF had returned to preseizure values, resulted in attenuated brain phenobarbital uptake not different from controls for the first 30 min. These results are explained by disruption of the blood-brain barrier to phenobarbital during the early (hypertensive) phase of status epilepticus.
Department of Neurology, University of California, San Francisco 94143-0870.
R P
RP
Simon
J R
JR
Copeland
N L
NL
Benowitz
P
P
Jacob
J
J
Bronstein
D000818:Animals; D001640:Bicuculline; D001769:Blood; D001794:Blood Pressure; D001812:Blood-Brain Barrier; D001921:Brain / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004569:Electroencephalography; D005260:Female; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D010634:Phenobarbital / Q000097:blood / Q000493:pharmacokinetics*; D012756:Sheep; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
D007773:Lactates; D019344:Lactic Acid; D001640:Bicuculline; D010634:Phenobarbital