Phenobarbital
 NAME OF DRUG: Phenobarbital (Luminal, Donnatal, Kinesed, Quadrinal, Antrocol Elixir, Mudrane GG, Solfoton, Rexatal) |
| PHYSICAL CHARACTERISTICS:Phenobarbital is barbiturate derivative and is available as either the free acid or as the sodium salt. The acid form is a white crystalline powder that is slightly soluble in water. The salt is a hygroscopic powder that is soluble in water. |
| DOSAGE/OCCURRENCE/USAGE: Phenobarbital was first used as a daytime sedative and anticonvulsant. It is frequently used in combination with other drugs such as bronchodilators, vasodilators, analgesics, and anticholenergics. It available in an elixir or tablet form of 15-65 mg for oral use or in 65-130 mg/mL solution for intramuscular or intervenous injection. For the treatment of epilepsy, it is typically administered orally in doses of 60-200 mg daily, often with other anticonvulsant drugs. Because phenobarbital has a low oil/water partition coefficient, it accumulates slowly in the brain tissue and is eliminated slowly. It appears to have a longer half-life after repeated use. Phenobarbital is considered a long acting barbiturate. |
| BLOOD CONCENTRATIONS VS. DOSAGE: In one study, three subjects were given a single 30 mg oral dose. The average peak serum concentration produced was 700 ng/mL. The same dose was repeated for 21 days resulted in an average peak level of 8100 ng/mL. Subjects given a 600 mg dose of phenobarbital had an average peak blood concentration of 18000 ng/mL (range 12000-26000) 4.5 hours after administration. Epileptic patients who were taking 200 mg daily had a phenobarbital blood concentration that ranged from 16000-48000 ng/mL with an average of 29000 ng/mL. Plasma concentrations of 10000-30000 ng/mL are considered appropriate therapeutic levels for use as an anticonvulsant. Phenobarbital has an average plasma half-life of about 4 days. |
| URINE EXCRETION RATE: Phenobarbital is eliminated slowly. Depending on the dose, it can take several days to several weeks. Approximately 78-87% of a single dose is excreted in the urine. Of this, 25-33% is the unchanged drug. For patients on chronic phenobarbital therapy, 12-55% of the dose is excreted as the unchanged drug. |
| METABOLITES: N-glucosylphenobarbital, free or p-hydroxyphenobarbital. |
| TOXICITY: The lethal dose of phenobarbital varies with many factors. In general, an oral dose of 1 g can result in poisoning in an adult. As little as 6 g can be fatal. Blood concentrations in fatal cases range from 78000-266000 ng/mL. Phenobarbital has been among the most frequent of all drugs noted in accidental poisonings and suicides. Alcohol is synergistic. |
| REFERENCES: Baslet, R.C. Disposition of Toxic Drugs and Chemicals in Man,
Second Edition. Davis, Calif.: Biomedical Publications, 1982. Clarke, E.G.C. Isolation and Identification of Drugs. London: The Pharmaceutical Press, 1969. Shaw, Richard F., Finkle, Bryan S. Barbiturates Abused Monograph Series. Ed. Caplan, Yale H. Irving, Texas: Abbott Laboratories, 1994 |