Microsomal enzyme induction

Microsomal enzyme induction has been shown to be increased by both mirex and chlordecone in humans and/or experimental animals. Serum levels of chlordecone associated with enzyme induction in exposed workers were estimated to range from 100 to 500 pg/L (Guzelian 1985). 

Urinary D-glucaric acid levels have been shown to be a sensitive indicator of microsomal enzyme induction in workers exposed to chlordecone (Guzelian 1985). However, other substances such as barbiturates, phenytoin, chlorbutanol, aminopyrine, phenylbutazone, and contraceptive steroids as well as other organochlorinated pesticides also cause microsomal enzyme induction and cause changes in urinary D-glucaric acid (Morgan and Roan 1974). 

Duche JC, Barre J, Guinot P, Duchier J, Cournot A, Tillement JP. (1989). Effect of Ginkgo biloba extract on microsomal enzyme induction. Int J Clin Pharmacol Res. 9(3) 165-68. 

McLean AEM. 1970. The effect of protein deficiency and microsomal enzyme induction by DDT and phenobarbitone on the acute toxicity of chloroform and a pyrrolizidine alkaloid, retrorsine. Br J Exp Pathol 51 317-321. 

C8. Coltart, J., Howard, M., and Chamberlain, D., Myocardial and skeletal muscle concentrations of digoxin on long-term therapy. Brit. Med. J. 11, 318-319 (1972). C9. Conney, A. H., Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317-366 (1967). 

C8. Conney, A. H., Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317-366 (1967). 

Dannan GA, Sleight SD, Fraker PJ, et al. 1982. Liver microsomal enzyme induction and toxicity studies with 2,4,5,3, 4 -pentabromobiphenyl. Toxicol Appl Phannacol 64 187-203. 

Shen ES, Guengerich FP, Olson JR. 1989. Biphasic response for hepatic microsomal enzyme induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J and DBA/2J mice. Biochem Pharmacol... 

Prescott LF, Critchley JAJH, Bulali-Mood M, et al. Effects of microsomal enzyme induction on paracetamol metabolism in man. Br J Clin Pharmacol 1981 12 149-153. 

Snyder, R. (2000) Profiles in toxicology microsomal enzyme induction. Toxicol. Sci. 55 233-234. 

Ventricular dysrhythmias can occur Hepatic microsomal enzyme induction Inhibition of metabolism... 

Particularly likely to occur when a tricyclic drug, a phenothiazine, and a antiparkinsonian drug are prescribed concurrently Tricyclic drugs can interfere with the metabolism of oral anticoagulants Convulsive threshold lowered Hepatic microsomal enzyme induction Hypertension should be controlled with diuretics, p-blockers, or vasodilators before treatment of depression... 

Conney AH. Pharmacological Implications of microsomal enzyme Induction. Pharmacol Rev 1967 19(3) 317-66. 

Microsomal enzyme induction may shorten the half-life of rifampin and decrease drug concentrations of concurrently administered... 

Chlorpromazine is strongly bound to protein, crosses blood-brain barrier, and concentrates in the brain against plasma gradient. More than 90% of the drug in plasma is bound to proteins, is metabolized in the liver, and is excreted in both urine and feces. There is some evidence that chlorpromazine can cause hepatic microsomal enzyme induction, which indicates that it may accelerate its own metabolism. 

In a subacute study, both male and female rats were fed diets containing octachlorostyrene at 0.5, 5.0, 50, and 500 mg kg for 28 days. Histological changes were observed in the liver and thyroid of rats exposed to doses equal to or greater than 5 mgkg. Hepatic microsomal enzyme induction and liver hypertrophy were observed in the two highest dose groups. At 500 mg kg there was an increase in... 

Key Words environmental regulation of xenobiotic metabolism, microsomal enzyme induction, activation of microsomal enzymes, drug-drug interactions, diet-drug interactions... 

Drug interactions secondary to microsomal, enzyme induction are frequent. 

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