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Metabolism of barbiturates in man
Author(s) -
Mark Lester C.
Publication year - 1963
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt196344504
Subject(s) - barbiturate , metabolism , pharmacology , chemistry , drug , biotransformation , drug metabolism , in vivo , demethylation , enzyme , biochemistry , medicine , biology , gene expression , microbiology and biotechnology , gene , dna methylation
Barbiturate effeets in man are limited by various proeesses. These include redistribution of unehanged drug within the body, development of toleranee, renal exeretion, and metabolie transformation. Biotransformation of barbiturates is mediated primarily by mierosomal enzyme systems residing in the liver. Yet, beeause of the abundant reserve eapacity of this organ, barbiturates need rwt be withheld from patients with liver disease unless the aeeompanying funetional impairment is extreme. Side ehain oxidation is the major meehanism of inactivation of barbiturates in vivo; 5‐dealkylation has also been deseribed. Ring cleavage, of theoretieal import, has still to be demonstrated in man. The products of other metabolie pathways sueh as N‐demethylation, desulfuration and (if verified) N‐methylation retain pharmacologic activity; these are not mechanisms for termination of barbiturate effect. Barbiturates may conveniently be divided into two groups according to whether their rate of metabolism is measured in days (long‐ and medium‐acting barbiturates) or in hours (anesthetie and short‐acting barbiturates). None is metabolized rapidly. Aeeeleration of mierosomal enzyme activity indueed by drugs and other eompounds, amply documented in animals, may ultimately prove a signifieant factor in barbiturate metabolism in man, whose drug history is often complex.