Barbiturates are weak acids that are absorbed and rapidly distributed to all tissues and fluids, with high concentrations in the brain, liver, and kidneys. Lipid solubility of the barbiturates is the dominant factor in their distribution within the body. The more lipid soluble the barbiturate, the more rapidly it penetrates all tissues of the body. Barbiturates are bound to plasma and tissue proteins to a varying degree, with the degree of binding increasing directly as a function of lipid solubility. Phenobarbital has the lowest lipid solubility, lowest plasma binding, lowest brain protein binding, the longest delay in onset of activity, and the longest duration of action. At the opposite extreme is secobarbital, which has the highest lipid solubility, highest plasma protein binding, highest brain protein binding, the shortest delay in onset of activity, and the shortest duration of action.
Secobarbital is metabolized by the liver via penultimate oxidation of the 1-methylbutyl substituent to form 5-allyl-5(3'-hydroxy-1'-methylbutyl)barbituric acid (hydroxysecobarbital), the major metabolite. Oxidation of the allyl substituent may also occur to form 5-[2',3'-dihydroxypropyl-5-(1'-methylbutyl)]barbituric acid (secodiol). These inactive metabolites are excreted in urine unchanged or as glucuronide conjugates. Hydroxysecobarbital may also be further oxidized to a ketone or a carboxylic acid. The allyl substituent at C 5 may be removed, and small quantities of the resulting 5-(1'-methylbutyl)barbituric acid metabolite have been found in urine.
Approximately 90% of an oral dose of secobarbital is absorbed from the GI tract within 2 hours after ingestion, and peak plasma concentrations are reached within 2-4 hours. Virtually all of the drug is absorbed following rectal administration.
Barbiturates are absorbed in varying degrees following oral, rectal, or im administration. The sodium salts are more rapidly absorbed by all routes of administration than are the acids. The rate of oral absorption is increased when the sodium salt is ingested as a dilute solution or taken on an empty stomach. Alcohol also enhances the rate of absorption, possibly by increasing blood flow through the gastric mucosa. /Barbiturates General Statement/