[Hepatic mono-oxygenases].
Most drugs and xenobiotics are lipid-soluble compounds that need to be transformed into more polar water-soluble molecules by a system of hepatic monoxygenases in order to be excreted by the kidney and the liver. This system is also called cytochrome P-450. It is found in animals, as well as plants. It is located in the cellular endoplasmic reticulum of numerous tissues, but it is most active in the liver. It is made up of several isoenzymes differing from one another by the structure of their apoproteins, their immunological characteristics and their affinity for various substrates. Cytochrome P-450 has great variability, being influenced by exogenous factors (drug intake, ionizing radiation, stress, diet) and individual endogenous factors (age, sex, genetic factors). Several non specific tests exploring the system are available. They include: direct investigations carried out on liver biopsies, which are seldom used in clinical practice, and indirect investigations, such as the measurement of the clearance of exogenous substances, of urinary metabolites of endogenous substances and of specific enzymes. Induction and inhibition of microsomal activity are of the utmost interest to the clinician in various fields such as toxicology, carcinogenesis, drug interactions or drug habituation, metabolic regulations and maintenance of body homeostasis. Seven classes of enzyme inducers have been defined, but the exact mechanism of this has only been identified for two of them (the barbiturate and polycyclic hydrocarbon groups). Several drugs have been identified as enzyme inhibitors, the best known to the anaesthesiologist being macrolide antibiotics, imidazole derivatives, cimetidine, chloramphenicol and isonazide.(ABSTRACT TRUNCATED AT 250 WORDS)
Robillart
A
A
Département d'Anesthésiologie, Hospices Civils de Strasbourg.
Zeisser
M
M
Vailly
B
B
Dupeyron
J P
JP
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000096:biosynthesis; D004347:Drug Interactions; D004790:Enzyme Induction; D004791:Enzyme Inhibitors; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D004364:Pharmaceutical Preparations; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System
Les monooxygénases hépatiques.