Hepatic elimination of diazepam: interactions with albumin, desflurane and sevoflurane. 1993

O Dale, and E J Frink, and L Thommesen, and A J Gandolfi
University of Trondheim, Department of Pharmacology and Toxicology, University Clinic, Norway.

We have studied the effect of sevoflurane and desflurane on the hepatic elimination of diazepam, by incubating slices of rat livers in a closed system. Protein free and protein containing (albumin 10 g litre-1) buffers were used to examine the effect of the anaesthetics on enzyme activity and diazepam binding to albumin. Both anaesthetics (in concentrations of 0.5, 1.5 and 3.0 mmol litre-1) reduced the elimination of diazepam slightly in the absence of albumin, while the presence of the protein increased elimination to a maximum of 30% at the greatest concentration of the anaesthetics. These data support previous observations that volatile anaesthetics may interact pharmacokinetically with both liver enzyme activity and drug binding to albumin.

UI MeSH Term Description Entries
D007530 Isoflurane A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008738 Methyl Ethers A group of compounds that contain the general formula R-OCH3. Ethers, Methyl
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D003975 Diazepam A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,Apaurin,Diazemuls,Faustan,Relanium,Seduxen,Sibazon,Stesolid,Valium
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004987 Ethers Organic compounds having two alkyl or aryl groups bonded to an oxygen atom, as in the formula R1–O–R2.
D000077149 Sevoflurane A non-explosive inhalation anesthetic used in the induction and maintenance of general anesthesia. It does not cause respiratory irritation and may also prevent PLATELET AGGREGATION. BAX 3084,Fluoromethyl Hexafluoroisopropyl Ether,Fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl Ether,Sevorane,Ultane
D000077335 Desflurane A fluorinated ether that is used as a volatile anesthetic for maintenance of general anesthesia. 1,2,2,2-Tetrafluoroethyl difluoromethyl ether,I 653,I-653,I653,Suprane

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