How does phenobarbital penetrate the brain during status epilepticus compared to a healthy brain?

Phenobarbital has low lipid solubility, which might appear to be a disadvantage for emergency treatment. However, studies have investigated its brain uptake under different conditions.

Preclinical studies and human trials suggest that brain uptake of phenobarbital in status epilepticus is much faster than in the healthy brain. This faster entry into the brain during status and preferential concentration for a long time is attributed to hyperperfusion in the early stages, systemic hypertension with increased mean arterial pressure, and a decrease in pH due to metabolic acidosis and lactate accumulation. Maximum brain concentrations were reached at 3 minutes with phenobarbital, compared to 1 minute with diazepam and 6 minutes with phenytoin in cat brain studies.