Drug-metabolizing enzyme system

Vij AG, Satija NK, Flora SJS. 1998. Lead induced disorders in hematopoietic and drug metabolizing enzyme system and their protection by ascorbic acid supplementation. Biomed Environ Sci 11 7-14. 

Bend, J. R., Pohl, R. J., and Fouts, J. R. Some properties of the microsomal drug-metabolizing enzyme system in the little skate, Rada evinaoea. Bull. Mt. Desert Island Biol. Lab. (1972) 12 9-12. 

Because trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug interactions that may alter trimetrexate plasma concentrations, which include erythromycin, rifampin, rifabutin, ketoconazole, fluconazole, cimetidine, nitrogen substituted imidazole drugs (eg, clotrimazole, ketoconazole, miconazole). 

Cheadwick RW, Copeland MF, Carlson GP, et al. 1988. Comparison of in vitro methods for assessing the effects of carbon tetrachloride on the hepatic drug-metabolizing enzyme system. Toxicol Lett 42 309-316. 

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

Mitotane, being closely related to the organochlo-rine insecticides, shares its inductive effects on the fiver microsomal drug-metabolizing enzyme system, and its use may therefore alter the requirement for concomitantly administered drugs that are also metabolized by this pathway. 

Metabolic transformation to more water-soluble metabolites is necessary for clearance of sedative-hypnotics from the body. The microsomal drug-metabolizing enzyme systems of the liver are most important in this regard, so elimination half-life of these drugs depends mainly on the rate of their metabolic transformation. 

Interactions involving changes in the activity of hepatic drug-metabolizing enzyme systems have been discussed (see also Chapters 4 and 66). 

The hepatic and renal toxicities of chloroform are selectively modified by induction of the drug-metabolizing enzyme systems in those organs (ref. 39) and the production of phosgene is strongly indicated (ref. 40). 

Kluwe, W.M., K.M. McCormack and J.B. Hook, "Selective Modification of Renal and Hepatic Toxicities of Chloroform by Induction of Drug-Metabolizing Enzyme Systems in Kidney... 

Remmer H (1972) Induction of drug metabolizing enzyme system in the liver. Eur J Clin Pharmacol 5 116-136 Simon P, Chermat R, Doare L et al. (1992) Interactions im-prevues de divers psychotropes avec les effets du barbital et du pentobarbital chez la souris. J Pharmacol 13 241-252... 

Arif JM, Khan SG, Mahmood N, et al. 1994. Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system. Environ Health Perspect Suppl 102 181-183. 

Alcohol plays an important role in the metabolism of foreign substances and is responsible for numerous interactions with drugs. A special type of cytochrome P 450 (P 450 II E 1) is induced by the chronic intake of alcohol. This subtype may influence other drug-metabolizing enzyme systems and possibly account for the carcinogenicity of dimethylnitrosamine in the gastrointestinal tract. 

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