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The metabolism of some barbiturate drugs: Factors affecting the metabolism of barbiturates.

Ioannides, Costas. (1973) The metabolism of some barbiturate drugs: Factors affecting the metabolism of barbiturates. Doctoral thesis, University of Surrey (United Kingdom)..

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The ability of a compound to induce the rat hepatic microsomal drug metabolizing enzymes was investigated using a series of commonly prescribed barbiturates. The biological half-life of these barbiturates was also determined in the rat using a sensitive gas-liquid chromatographic method. It was found that inductive ability depends on rate of metabolism of the compound and therefore on its chemical properties. Evidence is presented supporting the theory that ethanol is not a substrate of the enzyme system known to detoxify a diversity of compounds. The effect of chronic and acute ethanol administration on the mixed-function oxidase is investigated. The metabolic interaction of ethanol with barbiturates is studied both in vivo and in vitro. Ethanol is shown to potentiate the inductive effect of the barbiturates. Possible mechanisms of interaction are discussed. The interaction of barbiturates with imipramine is examined in vivo and imipramine is shown to inhibit the metabolism of pentobarbitone. The importance of the allyl group in the chemical induction of porphyria is considered using a variety of allyl group containing compounds. Porphyrogenicity of a compound is compared with its ability to induce drug metabolism. It is shown that compounds increasing the level of cytochrome P-450 in the microsomes do not necessarily induce delta-aminolaevulinic acid synthetase and vice versa. Finally the use of formic acid vapour in the carrier gas in gas liquid chromatography is critically considered. Formic acid is shown to reduce adsorption of polar compounds on stationary phase of the column and thus improves the limit of quantitation. Evidence is presented for possible mechanisms.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
Ioannides, Costas.
Date : 1973
Contributors :
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1973.
Depositing User : EPrints Services
Date Deposited : 22 Jun 2018 13:02
Last Modified : 06 Nov 2018 16:52

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