Brevital (Methohexital Sodium) - Description and Clinical Pharmacology

CIV

For Intravenous Use in Adults

For Rectal and Intramuscular Use Only in Pediatric Patients

DESCRIPTION

Brevital^® Sodium (Methohexital Sodium for Injection, USP) is 2,4,6 (1 H, 3 H, 5 H)-Pyrimidinetrione, 1-methyl-5-(1-methyl-2-pentynyl)-5-(2-propenyl)-, (±)-, monosodium salt and has the empirical formula C₁₄H₁₇N₂NaO₃. Its molecular weight is 284.29.

The structural formula is as follows:

Methohexital sodium is a rapid, ultrashort-acting barbiturate anesthetic. Methohexital sodium for injection is a freeze-dried, sterile, nonpyrogenic mixture of methohexital sodium with 6% anhydrous sodium carbonate added as a buffer. It contains not less than 90% and not more than 110% of the labeled amount of methohexital sodium. It occurs as a white, freeze-dried plug that is freely soluble in water.

This product is oxygen sensitive. The pH of the 1% solution is between 10 and 11; the pH of the 0.2% solution in 5% dextrose is between 9.5 and 10.5.

Methohexital sodium may be administered by direct intravenous injection or continuous intravenous drip, intramuscular or rectal routes (see PRECAUTIONS—Pediatric Use). Reconstituting instructions vary depending on the route of administration (see DOSAGE AND ADMINISTRATION).

CLINICAL PHARMACOLOGY

Compared with thiamylal and thiopental, methohexital is at least twice as potent on a weight basis, and its duration of action is only about half as long. Although the metabolic fate of methohexital in the body is not clear, the drug does not appear to concentrate in fat depots to the extent that other barbiturate anesthetics do. Thus, cumulative effects are fewer and recovery is more rapid with methohexital than with thiobarbiturates. In experimental animals, the drug cannot be detected in the blood 24 hours after administration.

Methohexital differs chemically from the established barbiturate anesthetics in that it contains no sulfur. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.

Intravenous administration of methohexital results in rapid uptake by the brain (within 30 seconds) and rapid induction of sleep.

Following intramuscular administration to pediatric patients, the onset of sleep occurs in 2 to 10 minutes. A plasma concentration of 3 µg/mL was achieved in pediatric patients 15 minutes after an intramuscular dose (10 mg/kg) of a 5% solution. Following rectal administration to pediatric patients, the onset of sleep occurs in 5 to 15 minutes. Plasma methohexital concentrations achieved following rectal administration tend to increase both with dose and with the use of more dilute solution concentrations when using the same dose. A 25 mg/kg dose of a 1% methohexital solution yielded plasma concentrations of 6.9 to 7.9 µg/mL 15 minutes after dosing. The absolute bioavailability of rectal methohexital sodium is 17%.

With single doses, the rate of redistribution determines duration of pharmacologic effect. Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity. Excretion occurs via the kidneys through glomerular filtration.