Phenobarbital is well absorbed from a variety of oral formulations, with peak concentrations reached in 2 to 12 hours. The bulk of phenobarbital is absorbed from the small intestine, where the un-ionized fraction is smaller but intraluminal dwell time is longer.

Phenobarbital disseminates into all body tissues but is only 40–50% plasma protein–bound. It is eliminated by a first-order process and has a low extraction ratio.

In the liver, phenobarbital is parahydroxylated and subsequently conjugated to glucuronic acid. The extent of glucuronide formation of phenobarbital varies widely. About 60–80% of the drug is metabolized by the liver, but alkalinization of the urine increases the amount of phenobarbital excreted unchanged by the kidney.5,6

Effects of liver disease

Although a significant amount of phenobarbital is excreted unchanged in the urine, the clearance of phenobarbital is altered in patients with liver disease. In cirrhotic patients, the half-life of phenobarbital is 130 ± 15 hours, compared to 86 ± 3 hours in healthy controls. The half-life of only one dose of phenobarbital is not altered in patients with acute hepatitis, however. Patients with cirrhosis have a decreased ability to form the parahydroxy metabolite of phenobarbital.7 It is unlikely that there are any clinically relevant changes in protein binding of phenobarbital in patients with liver disease.

Effects of GI disease

The presence of food and neutralizing agents or the occurrence of rapid gastric emptying slows phenobarbital absorption.6Therefore, GI disease may alter the absorption of phenobarbital.

Adapted from: Garnett WR. Gastrointestinal and hepatic disease. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;63-74.
With permission from Elsevier ( 

Reviewed By: 
Steven C. Schachter, MD
Monday, March 1, 2004