Microsomal drug-metabolizing enzymes

Riviere, J.L., J. Bach, and G. Grolleau. 1983. Effect of pyrethroid insecticides and N-(3,5-dichlorophenyl) dicarboximide fungicides on microsomal drug-metabolizing enzymes in the Japanese quail (Cotumix cotumix). Bull. Environ. Contam. Toxicol. 31 479-485. 

Campbell, M.A., S. Bandiera, L. Robertson, A. Parkinson, and S. Safe. 1983. Hepta-, hexa-, tetra- and dichloronaphthalene congeners as inducers of hepatic microsomal drug-metabolizing enzymes. Toxicology 26 193-205. 

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. 

Phenobarbital is effective orally and is distributed widely throughout the body. It is metabolized by microsomal drug-metabolizing enzymes, but up to 50% of the parent drug is excreted unchanged by the kidneys. Primidone is metabolized to phenobarbital and phenyl-ethylmalonamide. The latter metabolite has anticonvulsant activity, but most of the anticonvulsant efficacy of primidone is due to the phenobarbital that is produced. 

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. 

Induction of hepatic microsomal drug metabolizing enzymes. Additive central nervous system depression with other central nervous system depressants. 

Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not.) May inhibit the renal tubular secretion of weak bases. 

Inhibits hepatic microsomal drug-metabolizing enzymes. Inhibits aldehyde dehydrogenase. 

Goldstein JA, Linko PC, Levy LA, et al. 1979. A comparison of a commercial polybrominated biphenyl mixture, 2,4,5,2, 4, 5 -hexabromobiphenyl and 2,3,6,7-tetrabromonaphihalene as inducers of liver microsomal drug-metabolizing enzymes. Biochem Pharmacol 28 2947-2956. 

Robertson LW, Parkinson A, Bandicra S, et al. 1981. Potent induction of rat liver microsomal, drug-metabolizing enzymes by 2,3,3, 4,4, 5-hexabromobiphenyl, a component of Firemaster. Chem Biol Interact 35 13-24. 

Inhibits hepatic microsomal drug-metabolizing enzymes. (Ranitidine, famotidine, and nizatidine do not appear to do so.) May inhibit the renal tubular secretion of weak bases. Purportedly reduces hepatic blood flow, thus reducing first-pass metabolism of highly extracted drugs. (However, the ability of cimetidine to affect hepatic blood... 

Beierschmitt, W. P, McNeish, J. D., Griffiths, 1C J., Nagahisa, A., Nakane, M. and Amacher, D. E. (2001) Induction of hepatic microsomal drug-metabolizing enzymes by inhibitors of 5-lipoxygenase (5-LO) studies in rats and 5-LO knockout mice. Toxicol Sci 63,15-21. 

St John s wort can cause drug interactions by inducing hepatic microsomal drug-metabolizing enzymes or the drug transporter P-glycoprotein, which causes a net efflux of substrates, such as amitriptyline, from intestinal epithelial cells into the gut lumen (SEDA-24,12). In 12 patients (9 women, 3 men) the addition of St John s wort 900 mg/ day to amitriptyline 150 mg/day led to a 20% reduction in plasma amitriptyline concentrations, while nortriptyline concentrations were almost halved (210). 

Phenytoin induces hepatic microsomal drug-metabolizing enzymes and thus reduces concentrations of haloperidol (663,664), thioridazine (664), and tiotixene (665). In two patients phenytoin reduced plasma clozapine concentrations and worsened psychosis (666). 

Adaptive Enzyme Theory. The aliesterases are largely found in the microsomes of rat liver cells (44). Recently Hart and Fouts (51,52, 67-69) have presented evidence that in vivo administration of chlordan or chemically related DDT stimulates the activity of hepatic microsomal drug-metabolizing enzymes, as evidenced by proliferation of smooth-surfaced endoplasmic reticulum (SER) which was first noted with phenobarbital. Several reviews of hepatic drug metabolism... 

The metabolism of quinidine is enhanced by drugs that induce hepatic microsomal drug-metabolizing enzymes (67), such as rifampicin (77) and phenytoin and pheno-barbital (78). This leads to an increase in the first-pass metabolism of quinidine, and thus increased requirements of oral quinidine but little change in intravenous dosages. 

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